Hypoxic Hepatocellular Carcinoma Cells Acquire Arsenic Trioxide Resistance by Upregulating HIF-1α Expression
Background Although arsenic trioxide (ATO) is used in the treatment of advanced hepatocellular carcinoma (HCC) in clinical trials, it is not satisfactory in terms of improving HCC patients’ overall survival. Intratumoral hypoxia and overexpression of hypoxia-inducible factor-1α (HIF-1α) may result i...
Saved in:
Published in | Digestive diseases and sciences Vol. 67; no. 8; pp. 3806 - 3816 |
---|---|
Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Springer US
01.08.2022
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Abstract | Background
Although arsenic trioxide (ATO) is used in the treatment of advanced hepatocellular carcinoma (HCC) in clinical trials, it is not satisfactory in terms of improving HCC patients’ overall survival. Intratumoral hypoxia and overexpression of hypoxia-inducible factor-1α (HIF-1α) may result in ATO resistance and tumor progression.
Aims
We investigated the mechanisms involving HIF-1α expression and acquired ATO chemoresistance in HCC cells and mice.
Methods
The therapeutic effects of ATO in normoxic and hypoxic HCC cells were assessed using cell viability and apoptosis assays in vitro and a xenograft model in vivo. mRNA and protein expression of HIF-1α, P-glycoprotein, and VEGF were measured by qRT-PCR and western blotting. HIF-1α inhibition was performed to investigate the mechanism of ATO resistance. VEGF secretion was tested using ELISA and tube formation assays.
Results
Compared to normoxic cells, hypoxic HCC cells were more resistant to ATO, with higher IC
50
values and less apoptosis, and upregulated HIF-1α protein expression, accompanied with the enhancement of P-glycoprotein and VEGF synthesis after ATO treatment. VEGF secretion was elevated in the supernatant of ATO-treated HCC cells, and this change can potentiate angiogenesis in vitro. HIF-1α inhibition attenuated ATO resistance and angiogenesis and promoted the anticancer effects of ATO both in vitro and in vivo by downregulating therapy-induced P-glycoprotein and VEGF overexpression.
Conclusions
Hypoxic HCC cells acquire ATO resistance by upregulating HIF-1α levels; thus, combining ATO with a HIF-1α-targeting agent may lead to enhanced antitumor effects in HCC. |
---|---|
AbstractList | BACKGROUNDAlthough arsenic trioxide (ATO) is used in the treatment of advanced hepatocellular carcinoma (HCC) in clinical trials, it is not satisfactory in terms of improving HCC patients' overall survival. Intratumoral hypoxia and overexpression of hypoxia-inducible factor-1α (HIF-1α) may result in ATO resistance and tumor progression. AIMSWe investigated the mechanisms involving HIF-1α expression and acquired ATO chemoresistance in HCC cells and mice. METHODSThe therapeutic effects of ATO in normoxic and hypoxic HCC cells were assessed using cell viability and apoptosis assays in vitro and a xenograft model in vivo. mRNA and protein expression of HIF-1α, P-glycoprotein, and VEGF were measured by qRT-PCR and western blotting. HIF-1α inhibition was performed to investigate the mechanism of ATO resistance. VEGF secretion was tested using ELISA and tube formation assays. RESULTSCompared to normoxic cells, hypoxic HCC cells were more resistant to ATO, with higher IC50 values and less apoptosis, and upregulated HIF-1α protein expression, accompanied with the enhancement of P-glycoprotein and VEGF synthesis after ATO treatment. VEGF secretion was elevated in the supernatant of ATO-treated HCC cells, and this change can potentiate angiogenesis in vitro. HIF-1α inhibition attenuated ATO resistance and angiogenesis and promoted the anticancer effects of ATO both in vitro and in vivo by downregulating therapy-induced P-glycoprotein and VEGF overexpression. CONCLUSIONSHypoxic HCC cells acquire ATO resistance by upregulating HIF-1α levels; thus, combining ATO with a HIF-1α-targeting agent may lead to enhanced antitumor effects in HCC. Background Although arsenic trioxide (ATO) is used in the treatment of advanced hepatocellular carcinoma (HCC) in clinical trials, it is not satisfactory in terms of improving HCC patients’ overall survival. Intratumoral hypoxia and overexpression of hypoxia-inducible factor-1α (HIF-1α) may result in ATO resistance and tumor progression. Aims We investigated the mechanisms involving HIF-1α expression and acquired ATO chemoresistance in HCC cells and mice. Methods The therapeutic effects of ATO in normoxic and hypoxic HCC cells were assessed using cell viability and apoptosis assays in vitro and a xenograft model in vivo. mRNA and protein expression of HIF-1α, P-glycoprotein, and VEGF were measured by qRT-PCR and western blotting. HIF-1α inhibition was performed to investigate the mechanism of ATO resistance. VEGF secretion was tested using ELISA and tube formation assays. Results Compared to normoxic cells, hypoxic HCC cells were more resistant to ATO, with higher IC 50 values and less apoptosis, and upregulated HIF-1α protein expression, accompanied with the enhancement of P-glycoprotein and VEGF synthesis after ATO treatment. VEGF secretion was elevated in the supernatant of ATO-treated HCC cells, and this change can potentiate angiogenesis in vitro. HIF-1α inhibition attenuated ATO resistance and angiogenesis and promoted the anticancer effects of ATO both in vitro and in vivo by downregulating therapy-induced P-glycoprotein and VEGF overexpression. Conclusions Hypoxic HCC cells acquire ATO resistance by upregulating HIF-1α levels; thus, combining ATO with a HIF-1α-targeting agent may lead to enhanced antitumor effects in HCC. |
Author | Shan, Hong Jiang, Xiongying Li, Dan Chen, Dong Wang, Weidong Chen, Yaoting Li, Huiqing |
Author_xml | – sequence: 1 givenname: Yaoting orcidid: 0000-0003-1622-0764 surname: Chen fullname: Chen, Yaoting organization: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Interventional Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University – sequence: 2 givenname: Huiqing surname: Li fullname: Li, Huiqing organization: Health Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University – sequence: 3 givenname: Dong surname: Chen fullname: Chen, Dong organization: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Interventional Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University – sequence: 4 givenname: Xiongying surname: Jiang fullname: Jiang, Xiongying organization: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Interventional Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University – sequence: 5 givenname: Weidong surname: Wang fullname: Wang, Weidong organization: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation and Department of Interventional Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University – sequence: 6 givenname: Dan surname: Li fullname: Li, Dan organization: Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Institute of Interventional Radiology, Sun Yat-sen University – sequence: 7 givenname: Hong orcidid: 0000-0001-8222-4283 surname: Shan fullname: Shan, Hong email: shanhong_sysu@163.com organization: Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Institute of Interventional Radiology, Sun Yat-sen University, Department of Interventional Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University |
BookMark | eNp9kcFKJDEQhoMo7Kj7AnsKePHSWkm2k85xGNQRhIVFzyGJ1UNkJmmTbnB8q30Rn8mMIwge9lRF8f0_VfUfk8OYIhLyi8EFA1CXhYHk0ABnDSgOvHk9IDPWKtHwVnaHZAZM1p4x-YMcl_IEAFoxOSOb5XZIL8HTJQ52TB7X62ltM13Y7ENMG0sXdVTo3D9PISOd54Kx4vc5VNkj0r9YQhlt9Ejdlj4MGVfVYAxxRZe31w17-0evXuq0lJDiKTnq7brgz896Qh6ur-4Xy-buz83tYn7XeNHysfG9s613vepBOOY77bXT3rVo-SMy_dt2Xti27XuQwiEozUFw6VXHEHvnhDgh53vfIafnCctoNqHsbrMR01RMfQp0giklK3r2DX1KU451O8Nlp3WnWr0z5HvK51RKxt4MOWxs3hoGZpeA2SdgagLmIwHzWkViLyoVjivMX9b_Ub0D46aNmg |
CitedBy_id | crossref_primary_10_2478_aiht_2022_73_3669 crossref_primary_10_3389_fneur_2022_1001829 crossref_primary_10_3390_cancers14112740 |
Cites_doi | 10.1038/s41571-018-0073-4 10.1016/j.clinre.2014.04.004 10.1016/S0140-6736(18)30207-1 10.1172/JCI70212 10.1093/jnci/djm135 10.1038/bjc.2014.380 10.1056/NEJMoa0708857 10.1126/science.1127592 10.1002/hep.26224 10.1186/s12935-015-0269-y 10.1111/j.1349-7006.2006.00230.x 10.1016/j.blre.2010.04.001 10.1016/j.canlet.2015.06.014 10.1016/j.ccr.2009.01.027 10.1158/1078-0432.CCR-10-0068 10.1074/jbc.R900003200 10.1007/s10637-006-9004-9 10.1093/jnci/95.7.516 10.1038/nrc1187 10.1016/S1470-2045(15)00198-9 10.1053/j.gastro.2015.12.041 10.1182/blood.V96.4.1525 10.1245/s10434-010-1444-y 10.1016/S1470-2045(18)30146-3 10.1016/j.jhep.2014.08.025 10.1126/science.1183424 10.1038/nrc3627 10.1007/s12029-014-9617-8 10.1038/bjc.2013.787 10.1038/nrgastro.2014.10 10.1186/1476-4598-13-133 10.1371/journal.pone.0066416 |
ContentType | Journal Article |
Copyright | The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021 The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021. |
Copyright_xml | – notice: The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021 – notice: The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021. |
DBID | AAYXX CITATION 3V. 7RV 7X7 7XB 88E 8AO 8FI 8FJ 8FK ABUWG AFKRA AZQEC BENPR CCPQU FYUFA GHDGH K9- K9. KB0 M0R M0S M1P NAPCQ PQEST PQQKQ PQUKI PRINS 7X8 |
DOI | 10.1007/s10620-021-07202-z |
DatabaseName | CrossRef ProQuest Central (Corporate) Nursing & Allied Health Database Health & Medical Collection ProQuest Central (purchase pre-March 2016) Medical Database (Alumni Edition) ProQuest Pharma Collection Hospital Premium Collection Hospital Premium Collection (Alumni Edition) ProQuest Central (Alumni) (purchase pre-March 2016) ProQuest Central (Alumni) ProQuest Central ProQuest Central Essentials ProQuest Central ProQuest One Community College Health Research Premium Collection Health Research Premium Collection (Alumni) Consumer Health Database (Alumni Edition) ProQuest Health & Medical Complete (Alumni) Nursing & Allied Health Database (Alumni Edition) ProQuest Consumer Health Database Health & Medical Collection (Alumni Edition) Medical Database Nursing & Allied Health Premium ProQuest One Academic Eastern Edition (DO NOT USE) ProQuest One Academic ProQuest One Academic UKI Edition ProQuest Central China MEDLINE - Academic |
DatabaseTitle | CrossRef ProQuest Central Essentials ProQuest Family Health ProQuest One Academic Eastern Edition ProQuest Health & Medical Complete (Alumni) ProQuest Central (Alumni Edition) ProQuest One Community College ProQuest Nursing & Allied Health Source ProQuest Hospital Collection Health Research Premium Collection (Alumni) ProQuest Pharma Collection ProQuest Family Health (Alumni Edition) ProQuest Central China ProQuest Hospital Collection (Alumni) ProQuest Central Nursing & Allied Health Premium ProQuest Health & Medical Complete Health Research Premium Collection ProQuest Medical Library ProQuest One Academic UKI Edition Health and Medicine Complete (Alumni Edition) ProQuest Nursing & Allied Health Source (Alumni) ProQuest One Academic ProQuest Medical Library (Alumni) ProQuest Central (Alumni) MEDLINE - Academic |
DatabaseTitleList | MEDLINE - Academic ProQuest Central Essentials |
Database_xml | – sequence: 1 dbid: BENPR name: ProQuest Central url: https://www.proquest.com/central sourceTypes: Aggregation Database |
DeliveryMethod | fulltext_linktorsrc |
Discipline | Medicine |
EISSN | 1573-2568 |
EndPage | 3816 |
ExternalDocumentID | 10_1007_s10620_021_07202_z |
GrantInformation_xml | – fundername: Natural Science Foundation of Guangdong Province grantid: 2017A030313807 funderid: http://dx.doi.org/10.13039/501100003453 – fundername: National Natural Science Foundation of China grantid: 81620108017; 81771879 funderid: http://dx.doi.org/10.13039/501100001809 |
GroupedDBID | --- -53 -5E -5G -BR -EM -Y2 -~C -~X .55 .86 .GJ .VR 06C 06D 0R~ 0VY 199 1N0 1SB 2.D 203 28- 29G 29~ 2J2 2JN 2JY 2KG 2KM 2LR 2P1 2VQ 2~H 30V 354 3V. 4.4 406 408 409 40D 40E 476 53G 5GY 5QI 5RE 5VS 67Z 6NX 78A 7RV 7X7 88E 8AO 8FI 8FJ 8UJ 95- 95. 95~ 96X AABHQ AABYN AAFGU AAHNG AAIAL AAJKR AAKAS AAKSU AANXM AANZL AAPBV AAQQT AARHV AARTL AATNV AATVU AAUYE AAWCG AAWTL AAYFA AAYIU AAYQN AAYTO ABBBX ABBXA ABDZT ABECU ABFGW ABFTV ABHLI ABHQN ABIPD ABJNI ABJOX ABKAS ABKCH ABKTR ABMNI ABMQK ABNWP ABPLI ABPTK ABQBU ABSXP ABTEG ABTKH ABTMW ABULA ABUWG ABUWZ ABWNU ABXPI ACBMV ACBRV ACBXY ACBYP ACGFO ACGFS ACHSB ACHVE ACHXU ACIGE ACIHN ACIPQ ACKNC ACMDZ ACMLO ACOKC ACOMO ACREN ACTTH ACUDM ACVWB ACWMK ADBBV ADHHG ADHIR ADIMF ADINQ ADKNI ADKPE ADMDM ADOXG ADRFC ADTPH ADURQ ADYFF ADYOE ADZCM ADZKW AEAQA AEBTG AEEQQ AEFIE AEFTE AEGAL AEGNC AEJHL AEJRE AEKMD AENEX AEOHA AEPYU AESKC AESTI AETLH AEVLU AEVTX AEXYK AFAFS AFEXP AFFNX AFJLC AFKRA AFLOW AFNRJ AFQWF AFWTZ AFYQB AFZKB AGAYW AGDGC AGGBP AGGDS AGJBK AGKHE AGMZJ AGQMX AGWIL AGWZB AGYKE AHAVH AHBYD AHIZS AHKAY AHMBA AHSBF AHVUH AHYZX AIAKS AIIXL AILAN AIMYW AITGF AJBLW AJDOV AJRNO AKMHD AKQUC ALMA_UNASSIGNED_HOLDINGS ALWAN AMKLP AMTXH AMXSW AMYLF AMYQR AOCGG ARMRJ ASPBG AVWKF AXYYD AZFZN AZQEC B-. BA0 BBWZM BDATZ BENPR BGNMA BKEYQ BKNYI BPHCQ BVXVI CAG CCPQU COF CS3 CSCUP DDRTE DL5 DNIVK DPUIP DU5 EBD EBLON EBS EIOEI EJD EMOBN EN4 ESBYG EX3 F5P FEDTE FERAY FFXSO FIGPU FINBP FNLPD FRRFC FSGXE FWDCC FYUFA G-Y G-Z GGCAI GGRSB GJIRD GNWQR GQ6 GQ7 GQ8 GRRUI GXS HF~ HG5 HG6 HMCUK HMJXF HQYDN HRMNR HVGLF HZ~ I09 IAO IH2 IHE IJ- IKXTQ IMOTQ ITM IWAJR IXC IZIGR IZQ I~X I~Z J-C J0Z J5H JBSCW JCJTX JZLTJ K9- KDC KOV KOW KPH L7B LAK LLZTM M0R M1P M4Y MA- MJL N2Q N9A NAPCQ NB0 NDZJH NPVJJ NQJWS NU0 O9- O93 O9G O9I O9J OAM OHH OVD P19 P2P P9S PF0 PQQKQ PROAC PSQYO PT4 PT5 Q2X QOK QOR QOS R4E R89 R9I RHV RNI ROL RPX RRX RSV RXW RZC RZE RZK S16 S1Z S26 S27 S28 S37 S3B SAP SCLPG SDE SDH SDM SHX SISQX SJN SJYHP SMD SNE SNPRN SNX SOHCF SOJ SPISZ SRMVM SSLCW SSXJD STPWE SV3 SZ9 SZN T13 T16 TAE TEORI TSG TSK TSV TT1 TUC U2A U9L UG4 UKHRP UNUBA UOJIU UTJUX UZXMN VC2 VFIZW VVN W23 W48 WH7 WJK WK8 WOW X7M XOL YLTOR YOC Z45 Z7U Z7V Z7W Z7X Z81 Z82 Z83 Z87 Z88 Z8O Z8P Z8Q Z8R Z8V Z8W Z91 ZGI ZMTXR ZOVNA ZXP ZY1 ~EX ~KM AACDK AAEOY AAJBT AASML AAYXX ABAKF ACAOD ACDTI ACZOJ AEFQL AEMSY AFBBN AGQEE AGRTI AIGIU AJOOF ALIPV CITATION H13 IHR 7XB 8FK K9. PQEST PQUKI PRINS 7X8 |
ID | FETCH-LOGICAL-c352t-cfba5cbf7f03b1c89c9b9cb5ea2de194a8c3a55ff063be07920326c781eefbb33 |
IEDL.DBID | AGYKE |
ISSN | 0163-2116 |
IngestDate | Sat Aug 17 02:57:32 EDT 2024 Fri Sep 13 06:18:19 EDT 2024 Thu Sep 12 19:29:14 EDT 2024 Sat Dec 16 12:10:09 EST 2023 |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 8 |
Keywords | Hepatocellular carcinoma Arsenic trioxide HIF-1α Drug resistance Targeted therapy |
Language | English |
LinkModel | DirectLink |
MergedId | FETCHMERGED-LOGICAL-c352t-cfba5cbf7f03b1c89c9b9cb5ea2de194a8c3a55ff063be07920326c781eefbb33 |
Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ORCID | 0000-0003-1622-0764 0000-0001-8222-4283 |
PQID | 2689987593 |
PQPubID | 41056 |
PageCount | 11 |
ParticipantIDs | proquest_miscellaneous_2560831776 proquest_journals_2689987593 crossref_primary_10_1007_s10620_021_07202_z springer_journals_10_1007_s10620_021_07202_z |
PublicationCentury | 2000 |
PublicationDate | 2022-08-01 |
PublicationDateYYYYMMDD | 2022-08-01 |
PublicationDate_xml | – month: 08 year: 2022 text: 2022-08-01 day: 01 |
PublicationDecade | 2020 |
PublicationPlace | New York |
PublicationPlace_xml | – name: New York |
PublicationTitle | Digestive diseases and sciences |
PublicationTitleAbbrev | Dig Dis Sci |
PublicationYear | 2022 |
Publisher | Springer US Springer Nature B.V |
Publisher_xml | – name: Springer US – name: Springer Nature B.V |
References | Yeo, Chun, Cho (CR25) 2003; 95 Emadi, Gore (CR30) 2010; 24 Roboz, Dias, Lam (CR11) 2000; 96 Llovet, Montal, Sia, Finn (CR2) 2018; 15 Ahn, Chen, Chen (CR32) 2010; 16 Bruix, Takayama, Mazzaferro (CR4) 2015; 16 Rimassa, Assenat, Peck-Radosavljevic (CR1) 2018; 19 Liang, Zheng, Song (CR6) 2013; 57 Shaked, Ciarrocchi, Franco (CR29) 2006; 313 Kudo, Finn, Qin (CR7) 2018; 391 Lin, Hsu, Hsu, Hsu, Cheng, Yang (CR13) 2007; 25 Zhang, Yan, Zhou (CR8) 2010; 328 Subbarayan, Ardalan (CR14) 2014; 45 Yu, Chen, Chen, Ye, Hou, Liang (CR33) 2015; 15 Bruix, Reig, Sherman (CR3) 2016; 150 Liu, Hu, Ye, Ho, Chen, Lai (CR19) 2014; 110 Worns, Galle (CR17) 2014; 11 Semenza (CR21) 2003; 3 Tredan, Galmarini, Patel, Tannock (CR16) 2007; 99 Zhang, Yang, Sun (CR12) 2015; 366 Valenzuela, Glorieux, Stockis (CR9) 2014; 111 Zheng, Yin, Lu (CR15) 2014; 13 Platanias (CR10) 2009; 284 Cao, Yang, Wu, Wang, Jiang, Lu (CR20) 2014; 38 CR26 Welti, Loges, Dimmeler, Carmeliet (CR23) 2013; 123 Goel, Mercurio (CR24) 2013; 13 Llovet, Ricci, Mazzaferro (CR5) 2008; 359 Wilson, Tennant, McKeating (CR18) 2014; 61 Paez-Ribes, Allen, Hudock (CR22) 2009; 15 Liu, Pan, Dong (CR28) 2006; 97 Maeda, Hori, Nishitoh (CR31) 2001; 61 Tung, Cheng, Hsu (CR27) 2011; 18 B Liu (7202_CR28) 2006; 97 H Maeda (7202_CR31) 2001; 61 A Emadi (7202_CR30) 2010; 24 GL Semenza (7202_CR21) 2003; 3 J Welti (7202_CR23) 2013; 123 M Paez-Ribes (7202_CR22) 2009; 15 JN Tung (7202_CR27) 2011; 18 GK Wilson (7202_CR18) 2014; 61 S Cao (7202_CR20) 2014; 38 7202_CR26 RW Ahn (7202_CR32) 2010; 16 J Bruix (7202_CR4) 2015; 16 PR Subbarayan (7202_CR14) 2014; 45 XW Zhang (7202_CR8) 2010; 328 EJ Yeo (7202_CR25) 2003; 95 M Kudo (7202_CR7) 2018; 391 X Zhang (7202_CR12) 2015; 366 L Rimassa (7202_CR1) 2018; 19 LP Liu (7202_CR19) 2014; 110 T Zheng (7202_CR15) 2014; 13 LC Platanias (7202_CR10) 2009; 284 M Valenzuela (7202_CR9) 2014; 111 GJ Roboz (7202_CR11) 2000; 96 J Bruix (7202_CR3) 2016; 150 O Tredan (7202_CR16) 2007; 99 MA Worns (7202_CR17) 2014; 11 Y Liang (7202_CR6) 2013; 57 JM Llovet (7202_CR5) 2008; 359 Y Shaked (7202_CR29) 2006; 313 G Yu (7202_CR33) 2015; 15 JM Llovet (7202_CR2) 2018; 15 CC Lin (7202_CR13) 2007; 25 HL Goel (7202_CR24) 2013; 13 |
References_xml | – volume: 15 start-page: 599 year: 2018 end-page: 616 ident: CR2 article-title: Molecular therapies and precision medicine for hepatocellular carcinoma publication-title: Nat Rev Clin Oncol. doi: 10.1038/s41571-018-0073-4 contributor: fullname: Finn – volume: 38 start-page: 598 year: 2014 end-page: 603 ident: CR20 article-title: Protein expression of hypoxia-inducible factor-1 alpha and hepatocellular carcinoma: a systematic review with meta-analysis publication-title: Clin. Res Hepatol Gastroenterol. doi: 10.1016/j.clinre.2014.04.004 contributor: fullname: Lu – volume: 391 start-page: 1163 year: 2018 end-page: 1173 ident: CR7 article-title: Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial publication-title: Lancet doi: 10.1016/S0140-6736(18)30207-1 contributor: fullname: Qin – volume: 123 start-page: 3190 year: 2013 end-page: 3200 ident: CR23 article-title: Recent molecular discoveries in angiogenesis and antiangiogenic therapies in cancer publication-title: J Clin Investig. doi: 10.1172/JCI70212 contributor: fullname: Carmeliet – volume: 99 start-page: 1441 year: 2007 end-page: 1454 ident: CR16 article-title: Drug resistance and the solid tumor microenvironment publication-title: J Natl Cancer Inst. doi: 10.1093/jnci/djm135 contributor: fullname: Tannock – volume: 111 start-page: 874 year: 2014 end-page: 882 ident: CR9 article-title: Retinoic acid synergizes ATO-mediated cytotoxicity by precluding Nrf2 activity in AML cells publication-title: Br J Cancer doi: 10.1038/bjc.2014.380 contributor: fullname: Stockis – volume: 359 start-page: 378 year: 2008 end-page: 390 ident: CR5 article-title: Sorafenib in advanced hepatocellular carcinoma publication-title: N Engl J Med. doi: 10.1056/NEJMoa0708857 contributor: fullname: Mazzaferro – volume: 313 start-page: 1785 year: 2006 end-page: 1787 ident: CR29 article-title: Therapy-induced acute recruitment of circulating endothelial progenitor cells to tumors publication-title: Science doi: 10.1126/science.1127592 contributor: fullname: Franco – volume: 57 start-page: 1847 year: 2013 end-page: 1857 ident: CR6 article-title: Hypoxia-mediated sorafenib resistance can be overcome by EF24 through Von Hippel–Lindau tumor suppressor-dependent HIF-1alpha inhibition in hepatocellular carcinoma publication-title: Hepatology. doi: 10.1002/hep.26224 contributor: fullname: Song – volume: 15 start-page: 116 year: 2015 ident: CR33 article-title: Arsenic trioxide reduces chemo-resistance to 5-fluorouracil and cisplatin in HBx-HepG2 cells via complex mechanisms publication-title: Cancer Cell Int. doi: 10.1186/s12935-015-0269-y contributor: fullname: Liang – volume: 97 start-page: 675 year: 2006 end-page: 681 ident: CR28 article-title: Opposing effects of arsenic trioxide on hepatocellular carcinomas in mice publication-title: Cancer Sci doi: 10.1111/j.1349-7006.2006.00230.x contributor: fullname: Dong – volume: 24 start-page: 191 year: 2010 end-page: 199 ident: CR30 article-title: Arsenic trioxide—An old drug rediscovered publication-title: Blood Rev. doi: 10.1016/j.blre.2010.04.001 contributor: fullname: Gore – volume: 366 start-page: 112 year: 2015 end-page: 122 ident: CR12 article-title: Promyelocytic leukemia protein induces arsenic trioxide resistance through regulation of aldehyde dehydrogenase 3 family member A1 in hepatocellular carcinoma publication-title: Cancer Lett. doi: 10.1016/j.canlet.2015.06.014 contributor: fullname: Sun – volume: 15 start-page: 220 year: 2009 end-page: 231 ident: CR22 article-title: Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis publication-title: Cancer cell. doi: 10.1016/j.ccr.2009.01.027 contributor: fullname: Hudock – volume: 16 start-page: 3607 year: 2010 end-page: 3617 ident: CR32 article-title: A novel nanoparticulate formulation of arsenic trioxide with enhanced therapeutic efficacy in a murine model of breast cancer publication-title: Clin Cancer Res. doi: 10.1158/1078-0432.CCR-10-0068 contributor: fullname: Chen – volume: 284 start-page: 18583 year: 2009 end-page: 18587 ident: CR10 article-title: Biological responses to arsenic compounds publication-title: J Biol Chem. doi: 10.1074/jbc.R900003200 contributor: fullname: Platanias – volume: 25 start-page: 77 year: 2007 end-page: 84 ident: CR13 article-title: Arsenic trioxide in patients with hepatocellular carcinoma: a phase II trial publication-title: Investig New Drugs. doi: 10.1007/s10637-006-9004-9 contributor: fullname: Yang – volume: 95 start-page: 516 year: 2003 end-page: 525 ident: CR25 article-title: YC-1: a potential anticancer drug targeting hypoxia-inducible factor 1 publication-title: J Natl Cancer Inst. doi: 10.1093/jnci/95.7.516 contributor: fullname: Cho – volume: 3 start-page: 721 year: 2003 end-page: 732 ident: CR21 article-title: Targeting HIF-1 for cancer therapy publication-title: Nat Rev Cancer doi: 10.1038/nrc1187 contributor: fullname: Semenza – volume: 16 start-page: 1344 year: 2015 end-page: 1354 ident: CR4 article-title: Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial publication-title: Lancet Oncol. doi: 10.1016/S1470-2045(15)00198-9 contributor: fullname: Mazzaferro – volume: 150 start-page: 835 year: 2016 end-page: 853 ident: CR3 article-title: Evidence-based diagnosis, staging, and treatment of patients with hepatocellular carcinoma publication-title: Gastroenterology doi: 10.1053/j.gastro.2015.12.041 contributor: fullname: Sherman – volume: 61 start-page: 5432 year: 2001 end-page: 5440 ident: CR31 article-title: Tumor growth inhibition by arsenic trioxide (As2O3) in the orthotopic metastasis model of androgen-independent prostate cancer publication-title: Cancer Res contributor: fullname: Nishitoh – volume: 96 start-page: 1525 year: 2000 end-page: 1530 ident: CR11 article-title: Arsenic trioxide induces dose- and time-dependent apoptosis of endothelium and may exert an antileukemic effect via inhibition of angiogenesis publication-title: Blood. doi: 10.1182/blood.V96.4.1525 contributor: fullname: Lam – volume: 18 start-page: 1492 year: 2011 end-page: 1500 ident: CR27 article-title: Normoxically overexpressed hypoxia inducible factor 1-alpha is involved in arsenic trioxide resistance acquisition in hepatocellular carcinoma publication-title: Ann Surg Oncol. doi: 10.1245/s10434-010-1444-y contributor: fullname: Hsu – volume: 19 start-page: 682 year: 2018 end-page: 693 ident: CR1 article-title: Tivantinib for second-line treatment of MET-high, advanced hepatocellular carcinoma (METIV-HCC): a final analysis of a phase 3, randomised, placebo-controlled study publication-title: Lancet Oncol. doi: 10.1016/S1470-2045(18)30146-3 contributor: fullname: Peck-Radosavljevic – volume: 61 start-page: 1397 year: 2014 end-page: 1406 ident: CR18 article-title: Hypoxia inducible factors in liver disease and hepatocellular carcinoma: current understanding and future directions publication-title: J Hepatol. doi: 10.1016/j.jhep.2014.08.025 contributor: fullname: McKeating – volume: 328 start-page: 240 year: 2010 end-page: 243 ident: CR8 article-title: Arsenic trioxide controls the fate of the PML-RARalpha oncoprotein by directly binding PML publication-title: Science doi: 10.1126/science.1183424 contributor: fullname: Zhou – volume: 13 start-page: 871 year: 2013 end-page: 882 ident: CR24 article-title: VEGF targets the tumour cell publication-title: Nat Rev Cancer. doi: 10.1038/nrc3627 contributor: fullname: Mercurio – volume: 45 start-page: 363 year: 2014 end-page: 371 ident: CR14 article-title: In the war against solid tumors arsenic trioxide needs partners publication-title: J Gastrointest Cancer doi: 10.1007/s12029-014-9617-8 contributor: fullname: Ardalan – volume: 110 start-page: 1066 year: 2014 end-page: 1073 ident: CR19 article-title: HBx mutants differentially affect the activation of hypoxia-inducible factor-1alpha in hepatocellular carcinoma publication-title: Br J Cancer. doi: 10.1038/bjc.2013.787 contributor: fullname: Lai – volume: 11 start-page: 447 year: 2014 end-page: 452 ident: CR17 article-title: HCC therapies–lessons learned publication-title: Nat Rev Gastroenterol Hepatol. doi: 10.1038/nrgastro.2014.10 contributor: fullname: Galle – ident: CR26 – volume: 13 start-page: 133 year: 2014 ident: CR15 article-title: Nutlin-3 overcomes arsenic trioxide resistance and tumor metastasis mediated by mutant p53 in Hepatocellular carcinoma publication-title: Mol Cancer. doi: 10.1186/1476-4598-13-133 contributor: fullname: Lu – volume: 95 start-page: 516 year: 2003 ident: 7202_CR25 publication-title: J Natl Cancer Inst. doi: 10.1093/jnci/95.7.516 contributor: fullname: EJ Yeo – volume: 99 start-page: 1441 year: 2007 ident: 7202_CR16 publication-title: J Natl Cancer Inst. doi: 10.1093/jnci/djm135 contributor: fullname: O Tredan – volume: 19 start-page: 682 year: 2018 ident: 7202_CR1 publication-title: Lancet Oncol. doi: 10.1016/S1470-2045(18)30146-3 contributor: fullname: L Rimassa – volume: 61 start-page: 5432 year: 2001 ident: 7202_CR31 publication-title: Cancer Res contributor: fullname: H Maeda – volume: 96 start-page: 1525 year: 2000 ident: 7202_CR11 publication-title: Blood. doi: 10.1182/blood.V96.4.1525 contributor: fullname: GJ Roboz – volume: 45 start-page: 363 year: 2014 ident: 7202_CR14 publication-title: J Gastrointest Cancer doi: 10.1007/s12029-014-9617-8 contributor: fullname: PR Subbarayan – volume: 16 start-page: 3607 year: 2010 ident: 7202_CR32 publication-title: Clin Cancer Res. doi: 10.1158/1078-0432.CCR-10-0068 contributor: fullname: RW Ahn – volume: 328 start-page: 240 year: 2010 ident: 7202_CR8 publication-title: Science doi: 10.1126/science.1183424 contributor: fullname: XW Zhang – volume: 97 start-page: 675 year: 2006 ident: 7202_CR28 publication-title: Cancer Sci doi: 10.1111/j.1349-7006.2006.00230.x contributor: fullname: B Liu – volume: 13 start-page: 871 year: 2013 ident: 7202_CR24 publication-title: Nat Rev Cancer. doi: 10.1038/nrc3627 contributor: fullname: HL Goel – volume: 18 start-page: 1492 year: 2011 ident: 7202_CR27 publication-title: Ann Surg Oncol. doi: 10.1245/s10434-010-1444-y contributor: fullname: JN Tung – volume: 15 start-page: 116 year: 2015 ident: 7202_CR33 publication-title: Cancer Cell Int. doi: 10.1186/s12935-015-0269-y contributor: fullname: G Yu – volume: 15 start-page: 599 year: 2018 ident: 7202_CR2 publication-title: Nat Rev Clin Oncol. doi: 10.1038/s41571-018-0073-4 contributor: fullname: JM Llovet – volume: 57 start-page: 1847 year: 2013 ident: 7202_CR6 publication-title: Hepatology. doi: 10.1002/hep.26224 contributor: fullname: Y Liang – volume: 366 start-page: 112 year: 2015 ident: 7202_CR12 publication-title: Cancer Lett. doi: 10.1016/j.canlet.2015.06.014 contributor: fullname: X Zhang – volume: 391 start-page: 1163 year: 2018 ident: 7202_CR7 publication-title: Lancet doi: 10.1016/S0140-6736(18)30207-1 contributor: fullname: M Kudo – volume: 359 start-page: 378 year: 2008 ident: 7202_CR5 publication-title: N Engl J Med. doi: 10.1056/NEJMoa0708857 contributor: fullname: JM Llovet – volume: 150 start-page: 835 year: 2016 ident: 7202_CR3 publication-title: Gastroenterology doi: 10.1053/j.gastro.2015.12.041 contributor: fullname: J Bruix – volume: 16 start-page: 1344 year: 2015 ident: 7202_CR4 publication-title: Lancet Oncol. doi: 10.1016/S1470-2045(15)00198-9 contributor: fullname: J Bruix – volume: 13 start-page: 133 year: 2014 ident: 7202_CR15 publication-title: Mol Cancer. doi: 10.1186/1476-4598-13-133 contributor: fullname: T Zheng – volume: 61 start-page: 1397 year: 2014 ident: 7202_CR18 publication-title: J Hepatol. doi: 10.1016/j.jhep.2014.08.025 contributor: fullname: GK Wilson – volume: 284 start-page: 18583 year: 2009 ident: 7202_CR10 publication-title: J Biol Chem. doi: 10.1074/jbc.R900003200 contributor: fullname: LC Platanias – volume: 11 start-page: 447 year: 2014 ident: 7202_CR17 publication-title: Nat Rev Gastroenterol Hepatol. doi: 10.1038/nrgastro.2014.10 contributor: fullname: MA Worns – volume: 110 start-page: 1066 year: 2014 ident: 7202_CR19 publication-title: Br J Cancer. doi: 10.1038/bjc.2013.787 contributor: fullname: LP Liu – ident: 7202_CR26 doi: 10.1371/journal.pone.0066416 – volume: 111 start-page: 874 year: 2014 ident: 7202_CR9 publication-title: Br J Cancer doi: 10.1038/bjc.2014.380 contributor: fullname: M Valenzuela – volume: 313 start-page: 1785 year: 2006 ident: 7202_CR29 publication-title: Science doi: 10.1126/science.1127592 contributor: fullname: Y Shaked – volume: 15 start-page: 220 year: 2009 ident: 7202_CR22 publication-title: Cancer cell. doi: 10.1016/j.ccr.2009.01.027 contributor: fullname: M Paez-Ribes – volume: 123 start-page: 3190 year: 2013 ident: 7202_CR23 publication-title: J Clin Investig. doi: 10.1172/JCI70212 contributor: fullname: J Welti – volume: 25 start-page: 77 year: 2007 ident: 7202_CR13 publication-title: Investig New Drugs. doi: 10.1007/s10637-006-9004-9 contributor: fullname: CC Lin – volume: 38 start-page: 598 year: 2014 ident: 7202_CR20 publication-title: Clin. Res Hepatol Gastroenterol. doi: 10.1016/j.clinre.2014.04.004 contributor: fullname: S Cao – volume: 3 start-page: 721 year: 2003 ident: 7202_CR21 publication-title: Nat Rev Cancer doi: 10.1038/nrc1187 contributor: fullname: GL Semenza – volume: 24 start-page: 191 year: 2010 ident: 7202_CR30 publication-title: Blood Rev. doi: 10.1016/j.blre.2010.04.001 contributor: fullname: A Emadi |
SSID | ssj0009716 |
Score | 2.4340158 |
Snippet | Background
Although arsenic trioxide (ATO) is used in the treatment of advanced hepatocellular carcinoma (HCC) in clinical trials, it is not satisfactory in... BackgroundAlthough arsenic trioxide (ATO) is used in the treatment of advanced hepatocellular carcinoma (HCC) in clinical trials, it is not satisfactory in... BACKGROUNDAlthough arsenic trioxide (ATO) is used in the treatment of advanced hepatocellular carcinoma (HCC) in clinical trials, it is not satisfactory in... |
SourceID | proquest crossref springer |
SourceType | Aggregation Database Publisher |
StartPage | 3806 |
SubjectTerms | Angiogenesis Apoptosis Arsenic Biochemistry Gastroenterology Glycoproteins Hepatology Hypoxia Liver cancer Medicine Medicine & Public Health Oncology Original Article Protein expression Transplant Surgery |
SummonAdditionalLinks | – databaseName: Health & Medical Collection dbid: 7X7 link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV1fi9QwEB_OE8QX8S-unhLBNw27bdqkeZJjuaUK54Pcwr6VJJ3APVy77vbg7r6VX8TP5Ey3tSjoa5MmZTLN_CaZmR_Ae2uSaAuM0hJ2kOR_WWmDijKQdXMKM9R9Lb3zr7pcZ182-eYIyjEXhsMqxz2x36jrNvAZ-TzV7BmY3Kq583wKELr5p-13yfxRfM86kGncg_tJSrCCNNtszFR-1_QkqIRvlCSXRw_pM0MSnSYXikMVFial_eHuTxM14c6_rkp7C7R6DI8G6ChOD2v9BI6weQoPzofL8WdwVd5u25vLIEoyMV3LR_IcYyqWTBfUtFdOLOnRXpwGjv5FGmiPDXW_2F3SazWKb7hnNElqIPytWG93B556-hhRfl7J5OcPcXYzBM42z2G9OrtYlnJgU5CBQFYnQ_QuDz6auFA-CYUN1tvgc3RpjYnNXBGUy_MYCbR4XBjL3Oo6mCJBjN4r9QKOm7bBlyCSQhNsK7KYpj4LtXbUHFVN2GOBXNJvBh9GAVbbQ9GMaiqPzOKuSNxVL-7qbgYno4yr4QfaV9Nyz-Dd72ZSfRaea7C9pj6E1grCP0bP4OO4NtMQ_57x1f9nfA0PU05y6MP8TuC4213jG4IenX_ba9UvMbPW_Q priority: 102 providerName: ProQuest |
Title | Hypoxic Hepatocellular Carcinoma Cells Acquire Arsenic Trioxide Resistance by Upregulating HIF-1α Expression |
URI | https://link.springer.com/article/10.1007/s10620-021-07202-z https://www.proquest.com/docview/2689987593/abstract/ https://search.proquest.com/docview/2560831776 |
Volume | 67 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwlV1fa9swED_WFMZe2u4fS_8EDfbWqcSWLVmPSUjmbTSUkkD2ZCxFgjJqh8SBNt-qX6SfqSfHrrtue-iTwZJl-3Ty_c763R3AFyk8KyNjqUTsQNH_klRqZqlG65YyExhe5tI7H_N4GvyYhbMmjrsku9c7kuWH-kmsG0dPxzEKugI9drrZgd3QlaVuwW7v26-fwybXrigrniKYYRT9G17Fyvx7lD_tUQMyn-2LluZmtA-TOmhnyzL5fbYu1Jne_J3D8SVvcgB7Ffwkva2-vIVXJnsHr8-rDfb3cB3fLvKbK01iNFNF7n7rO54qGbiSQ1l-nZIBnlqRnnYMYoMDrUyG3SfLK7xsbsilWTlEiqpE1C2ZLpbbWvf4fCT-PqLe_R0Z3lTk2-wDTEfDySCmVUUGqhGoFVRblYZaWWG7THk6kloqqVVoUn9uPBmkkWZpGFqLwEeZrpCuPjvXIvKMsUox9hFaWZ6ZT0C8iCP0iwLr-yrQc55is2VzxC9d49ICtuG0npdksU28kTQplp0EE5RgUkow2bThuJ66pFqEq8TnzpkUoWRt-PzYjMvHCS_NTL7GPoj4IsRQgrfhaz1dzRD_v-Phy7ofwRvfBU6U1MFjaBXLtTlBOFOoDuyImeigEo_6_XGnUmY89ofji0tsnfq9B3O98ZQ |
link.rule.ids | 315,786,790,12083,21416,27957,27958,31754,31755,33779,33780,41116,41558,42185,42627,43345,43840,52146,52269,74102,74659 |
linkProvider | Springer Nature |
linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV1fa9swED-2FLa-jO4fzdZ2GvRtE4stW7aeShsS3D8JpSTQN2PJJ-hD7TROoe232hfZZ9rJUWY26F4tWTJ3su53p9P9AA5VEliVouWKsAMn_0txZYTlhqxbITBC2dbSm0xlNo_OruNrH3BrfFrlZk9sN-qyNi5G_iOUzjNIYiWOFnfcsUa501VPofEStiJBrkoPtk5G08urruxu0pKfEq4RnFwd6a_N-Mtzklwnl6IwSELaF57-Nk0d3vzniLS1POMdeOMhIzte6_gtvMDqHbya-EPx93CbPS7qhxvDMjItq9qF4l1uKRs6mqCqvi3YkB417Ni4rF-kgRqsqPtseUOvlciusHEoktTP9CObL5Zrfnr6GJadjnnw6ycbPfiE2eoDzMej2TDjnkWBGwJXK26sLmKjbWIHQgcmVUZpZXSMRVhioKIiNaKIY2sJrGgcJMpxqkuTpAGi1VqIj9Cr6gp3gQWpJLiWRjYMdWRKWVCzFSVhjgG6Un59-LYRYL5YF8vIu7LITtw5iTtvxZ0_9WFvI-Pc_zhN3qm5D1__NNOSd8IrKqzvqQ-htJRwTyL78H2jm26I52f89P8Zv8DrbDa5yC9Op-efYTt0Fx3aVL896K2W97hP8GOlD_wa-w2RZteW |
linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV1NT9wwEB1RKqFeEP1SF2jrSr21Fkmc2PGpQltWgRZUVay0tyh2xhIHkmWzSMC_4o_wmzrOehtRiV5jx47GE8-z_TwP4LNWsdM5Oq4JO3Baf2murXDcUnSrBKYo-1x6p2eymKYns2wW-E9doFWu58R-oq5b6_fIDxLpVwYq0-LABVrEr--Tb_Mr7hWk_ElrkNN4Bs8pSkZezUDN1JCAV_UyqIRwBKdFjwwXaMI1OkmLKE9WiFRCM8Td4yA1IM9_Dkv7GDTZge0AHtnharRfwgY2r2DrNByPv4bL4nbe3lxYVlCQWbZ-U96zTNnYCwY17WXFxvSoY4fW83-RGuqwoerniwt6rUb2GzuPJ8kRmLll0_lipVRPH8OK4wmPH-7Z0U2gzjZvYDo5Oh8XPOgpcEswa8mtM1VmjVMuEia2ubbaaGsyrJIaY51WuRVVljlHsMVgpLRXV5dW5TGiM0aIt7DZtA2-AxbnkoBbnrokMamtZUXFTtSEPiL0Sf1G8GVtwHK-SptRDgmSvblLMnfZm7u8G8H-2sZl-IW6chjwEXz6W0zO741XNdheUx3CazkhICVH8HU9NkMTT_e4-_8eP8IWOVf58_jsxx68SPyNh57ztw-by8U1viccsjQfegf7A9UR2lw |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Hypoxic+Hepatocellular+Carcinoma+Cells+Acquire+Arsenic+Trioxide+Resistance+by+Upregulating+HIF-1%CE%B1+Expression&rft.jtitle=Digestive+diseases+and+sciences&rft.au=Chen%2C+Yaoting&rft.au=Li%2C+Huiqing&rft.au=Chen%2C+Dong&rft.au=Jiang%2C+Xiongying&rft.date=2022-08-01&rft.pub=Springer+US&rft.issn=0163-2116&rft.eissn=1573-2568&rft.volume=67&rft.issue=8&rft.spage=3806&rft.epage=3816&rft_id=info:doi/10.1007%2Fs10620-021-07202-z&rft.externalDocID=10_1007_s10620_021_07202_z |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0163-2116&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0163-2116&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0163-2116&client=summon |