IGF-1R inhibition potentiates cytotoxic effects of chemotherapeutic agents in early stages of chemoresistant ovarian cancer cells

Highlights • IGF-1R expression elevates at early stages of chemoresistance in EOC cells. • PPP, an IGF-1R inhibitor exhibits maximal resistance reversal at early stages. • PPP with cisplatin, paclitaxel and both at low doses exert significant efficacy. • IGF-1R expression increases in ovarian cancer...

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Published inCancer letters Vol. 354; no. 2; pp. 254 - 262
Main Authors Singh, Ram K, Gaikwad, Snehal M, Jinager, Ankit, Chaudhury, Smrita, Maheshwari, Amita, Ray, Pritha
Format Journal Article
LanguageEnglish
Published Ireland Elsevier Ireland Ltd 28.11.2014
Elsevier Limited
Subjects
Adapter proteins
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Cancer therapies
Carcinoma, Ovarian Epithelial
Cell Line, Tumor
Chemoresistance
Chemotherapy
Cisplatin - administration & dosage
Cisplatin - pharmacology
Clinical trials
Cytotoxicity
Down-Regulation
Drug dosages
Drug Resistance, Neoplasm
Drug Synergism
Female
Hematology, Oncology and Palliative Medicine
Humans
IGF-1R signaling
Kinases
Ligands
Molecular Targeted Therapy
Neoplasm Staging
Neoplasms, Glandular and Epithelial - drug therapy
Neoplasms, Glandular and Epithelial - metabolism
Neoplasms, Glandular and Epithelial - pathology
Ovarian cancer
Ovarian Neoplasms - drug therapy
Ovarian Neoplasms - metabolism
Ovarian Neoplasms - pathology
Paclitaxel - administration & dosage
Paclitaxel - pharmacology
Podophyllotoxin - administration & dosage
Podophyllotoxin - analogs & derivatives
Podophyllotoxin - pharmacology
Proteasome Endopeptidase Complex - metabolism
Receptor, IGF Type 1 - antagonists & inhibitors
Receptor, IGF Type 1 - biosynthesis
Tumors
IGF-1R signaling
Chemoresistance
Ovarian cancer
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Abstract Highlights • IGF-1R expression elevates at early stages of chemoresistance in EOC cells. • PPP, an IGF-1R inhibitor exhibits maximal resistance reversal at early stages. • PPP with cisplatin, paclitaxel and both at low doses exert significant efficacy. • IGF-1R expression increases in ovarian cancer patients after chemotherapy.
AbstractList The kinetics and effect of hyper activated IGF-1R signaling is not well investigated during acquirement of platinum and taxol resistance in ovarian cancer cells. Herein we reported an upregulated IGF-1R expression in early stages of cisplatin paclitaxel and cisplatin-taxol resistance. Picropodophyllin, an IGF-1R inhibitor, alone and in combination with cisplatin, paclitaxel or both at lowest possible doses could reverse the resistance at early stages. Upregulated IGF-1R was also found in primary tumors of ovarian cancer patients after three to four cycles of platinum-taxol treatment. These findings indicate that a combination of cytotoxic agents and IGF-1R inhibitor is more effective at early stages of chemoresistant ovarian cancer.
•IGF-1R expression elevates at early stages of chemoresistance in EOC cells.•PPP, an IGF-1R inhibitor exhibits maximal resistance reversal at early stages.•PPP with cisplatin, paclitaxel and both at low doses exert significant efficacy.•IGF-1R expression increases in ovarian cancer patients after chemotherapy. The kinetics and effect of hyper activated IGF-1R signaling is not well investigated during acquirement of platinum and taxol resistance in ovarian cancer cells. Herein we reported an upregulated IGF-1R expression in early stages of cisplatin paclitaxel and cisplatin–taxol resistance. Picropodophyllin, an IGF-1R inhibitor, alone and in combination with cisplatin, paclitaxel or both at lowest possible doses could reverse the resistance at early stages. Upregulated IGF-1R was also found in primary tumors of ovarian cancer patients after three to four cycles of platinum–taxol treatment. These findings indicate that a combination of cytotoxic agents and IGF-1R inhibitor is more effective at early stages of chemoresistant ovarian cancer.
Highlights • IGF-1R expression elevates at early stages of chemoresistance in EOC cells. • PPP, an IGF-1R inhibitor exhibits maximal resistance reversal at early stages. • PPP with cisplatin, paclitaxel and both at low doses exert significant efficacy. • IGF-1R expression increases in ovarian cancer patients after chemotherapy.
Author Ray, Pritha
Singh, Ram K
Maheshwari, Amita
Gaikwad, Snehal M
Jinager, Ankit
Chaudhury, Smrita
Author_xml – sequence: 1
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  fullname: Maheshwari, Amita
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  fullname: Ray, Pritha
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2014 Elsevier Ireland Ltd
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Keywords IGF-1R signaling
Chemoresistance
Ovarian cancer
Language English
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SSID ssj0005475
Score 2.3987966
Snippet Highlights • IGF-1R expression elevates at early stages of chemoresistance in EOC cells. • PPP, an IGF-1R inhibitor exhibits maximal resistance reversal at...
•IGF-1R expression elevates at early stages of chemoresistance in EOC cells.•PPP, an IGF-1R inhibitor exhibits maximal resistance reversal at early stages.•PPP...
The kinetics and effect of hyper activated IGF-1R signaling is not well investigated during acquirement of platinum and taxol resistance in ovarian cancer...
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SubjectTerms Adapter proteins
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Cancer therapies
Carcinoma, Ovarian Epithelial
Cell Line, Tumor
Chemoresistance
Chemotherapy
Cisplatin - administration & dosage
Cisplatin - pharmacology
Clinical trials
Cytotoxicity
Down-Regulation
Drug dosages
Drug Resistance, Neoplasm
Drug Synergism
Female
Hematology, Oncology and Palliative Medicine
Humans
IGF-1R signaling
Kinases
Ligands
Molecular Targeted Therapy
Neoplasm Staging
Neoplasms, Glandular and Epithelial - drug therapy
Neoplasms, Glandular and Epithelial - metabolism
Neoplasms, Glandular and Epithelial - pathology
Ovarian cancer
Ovarian Neoplasms - drug therapy
Ovarian Neoplasms - metabolism
Ovarian Neoplasms - pathology
Paclitaxel - administration & dosage
Paclitaxel - pharmacology
Podophyllotoxin - administration & dosage
Podophyllotoxin - analogs & derivatives
Podophyllotoxin - pharmacology
Proteasome Endopeptidase Complex - metabolism
Receptor, IGF Type 1 - antagonists & inhibitors
Receptor, IGF Type 1 - biosynthesis
Tumors
Title IGF-1R inhibition potentiates cytotoxic effects of chemotherapeutic agents in early stages of chemoresistant ovarian cancer cells
URI https://www.clinicalkey.es/playcontent/1-s2.0-S0304383514004534
https://dx.doi.org/10.1016/j.canlet.2014.08.023
https://www.ncbi.nlm.nih.gov/pubmed/25157649
https://www.proquest.com/docview/1620243910
https://search.proquest.com/docview/1566822381
Volume 354
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