Label-Free Quantitative Proteomics Analysis of the Sorafenib Resistance in HepG2 Cells
Drug resistance of sorafenib seriously affects the treatment effect of late-stage hepatocellular carcinoma (HCC) patients. However, the precise mechanism of resistance to sorafenib remains unclear. Therefore, to obtain a deep understand of sorafenib resistance mechanisms and find potential therapeut...
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Published in | Journal of analysis and testing Vol. 6; no. 3; pp. 308 - 317 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
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Springer Nature Singapore
01.09.2022
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Abstract | Drug resistance of sorafenib seriously affects the treatment effect of late-stage hepatocellular carcinoma (HCC) patients. However, the precise mechanism of resistance to sorafenib remains unclear. Therefore, to obtain a deep understand of sorafenib resistance mechanisms and find potential therapeutic targets are very important for improving the clinical prognosis of HCC patients. In this study, a label-free quantitative proteomics method was performed to investigate the proteins differentially expressed between HepG2 and the sorafenib-acquired resistance HepG2 (HepG2-R) cells. In total, 84 differential expressed proteins were identified between the two cell lines. Bioinformatics analysis results demonstrated the dysregulated metabolic processes have a significant impact on the drug resistance of HepG2-R cells. Among them, the expression of Microsomal glutathione S-transferase 1 (MGST1) in two cell lines was further confirmed by western blot method. Moreover, colony formation assay and trypan blue dye assay results revealed that MGST1 is closely connected with the sorafenib resistance of HepG2-R cells, and the knockdown of MGST1 increased the sensitivity of sorafenib resistance HepG2-R cells to sorafenib treatment. In conclusion, these results lay a foundation for deciphering the mechanism for HCC sorafenib resistance and present a possibility of MGST1 serving as a therapeutic target for the treatment of sorafenib resistance HCC. |
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AbstractList | Drug resistance of sorafenib seriously affects the treatment effect of late-stage hepatocellular carcinoma (HCC) patients. However, the precise mechanism of resistance to sorafenib remains unclear. Therefore, to obtain a deep understand of sorafenib resistance mechanisms and find potential therapeutic targets are very important for improving the clinical prognosis of HCC patients. In this study, a label-free quantitative proteomics method was performed to investigate the proteins differentially expressed between HepG2 and the sorafenib-acquired resistance HepG2 (HepG2-R) cells. In total, 84 differential expressed proteins were identified between the two cell lines. Bioinformatics analysis results demonstrated the dysregulated metabolic processes have a significant impact on the drug resistance of HepG2-R cells. Among them, the expression of Microsomal glutathione S-transferase 1 (MGST1) in two cell lines was further confirmed by western blot method. Moreover, colony formation assay and trypan blue dye assay results revealed that MGST1 is closely connected with the sorafenib resistance of HepG2-R cells, and the knockdown of MGST1 increased the sensitivity of sorafenib resistance HepG2-R cells to sorafenib treatment. In conclusion, these results lay a foundation for deciphering the mechanism for HCC sorafenib resistance and present a possibility of MGST1 serving as a therapeutic target for the treatment of sorafenib resistance HCC. |
Author | Liang, Zhen Wang, Zi-Xuan Chu, Hong-Wei Zhang, Yu-Kui Yang, Kai-Guang Zhang, Li-Hua Zhao, Bao-Feng |
Author_xml | – sequence: 1 givenname: Zi-Xuan surname: Wang fullname: Wang, Zi-Xuan organization: CAS Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic R. & A. Center, Dalian Institute of Chemical Physics, Chinese Academy of Science, University of Chinese Academy of Sciences – sequence: 2 givenname: Hong-Wei surname: Chu fullname: Chu, Hong-Wei organization: CAS Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic R. & A. Center, Dalian Institute of Chemical Physics, Chinese Academy of Science, Zhang Dayu School of Chemistry, Dalian University of Technology – sequence: 3 givenname: Kai-Guang surname: Yang fullname: Yang, Kai-Guang organization: CAS Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic R. & A. Center, Dalian Institute of Chemical Physics, Chinese Academy of Science – sequence: 4 givenname: Bao-Feng surname: Zhao fullname: Zhao, Bao-Feng email: baofzhao@dicp.ac.cn organization: CAS Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic R. & A. Center, Dalian Institute of Chemical Physics, Chinese Academy of Science – sequence: 5 givenname: Zhen surname: Liang fullname: Liang, Zhen organization: CAS Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic R. & A. Center, Dalian Institute of Chemical Physics, Chinese Academy of Science – sequence: 6 givenname: Li-Hua surname: Zhang fullname: Zhang, Li-Hua organization: CAS Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic R. & A. Center, Dalian Institute of Chemical Physics, Chinese Academy of Science – sequence: 7 givenname: Yu-Kui surname: Zhang fullname: Zhang, Yu-Kui organization: CAS Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic R. & A. Center, Dalian Institute of Chemical Physics, Chinese Academy of Science, Zhang Dayu School of Chemistry, Dalian University of Technology |
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Cites_doi | 10.1038/sj.onc.1209373 10.1038/s41575-019-0186-y 10.1002/ijc.27604 10.3310/hta14Suppl1/03 10.1021/mp2000692 10.7150/jca.31448 10.1002/prca.201900080 10.3892/or.2018.6606 10.1016/j.canlet.2018.04.013 10.1074/jbc.275.17.13000 10.1038/nmeth.3901 10.21873/cgp.20080 10.1074/mcp.M114.046417 10.4161/cbt.8.20.9436 10.1074/mcp.TIR119.001827 10.3390/cancers12082116 10.7150/thno.25487 10.4254/wjh.v6.i10.752 10.1074/jbc.M009400200 10.1016/j.bbrc.2007.02.018 10.1016/j.canlet.2019.02.040 10.3389/fphar.2012.00005 10.3892/ol.2013.1768 10.1016/j.ejphar.2019.172883 10.3350/cmh.2019.0031 10.3892/ol.2015.3315 10.1093/carcin/bgab019 10.1002/cncr.28730 10.1016/0006-2952(84)90145-x 10.1158/0008-5472.Can-04-1443 |
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Keywords | Hepatocellular carcinoma Quantitative proteomics Drug resistance Sorafenib |
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Title | Label-Free Quantitative Proteomics Analysis of the Sorafenib Resistance in HepG2 Cells |
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