title: IGF-1R inhibition potentiates cytotoxic effects of chemotherapeutic agents in early stages of chemoresistant ovarian cancer cells.
abstract: 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.
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, Maharashtra, India.
authors.forename: Ram K
authors.initials: RK
authors.lastname: Singh
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, Maharashtra, India.
authors.forename: Snehal M
authors.initials: SM
authors.lastname: Gaikwad
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, Maharashtra, India.
authors.forename: Ankit
authors.initials: A
authors.lastname: Jinager
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, Maharashtra, India.
authors.forename: Smrita
authors.initials: S
authors.lastname: Chaudhury
authors.affiliation: Gynecologic Oncology, Tata Memorial Hospital, Dr. E Borges Road, Parel, Mumbai, Maharashtra, India.
authors.forename: Amita
authors.initials: A
authors.lastname: Maheshwari
authors.affiliation: Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, Maharashtra, India. Electronic address: pray@actrec.gov.in.
authors.forename: Pritha
authors.initials: P
authors.lastname: Ray
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology*; D011034:Podophyllotoxin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: C415032:picropodophyllin; D017526:Receptor, IGF Type 1; D046988:Proteasome Endopeptidase Complex; D011034:Podophyllotoxin; D017239:Paclitaxel; D002945:Cisplatin
keywords: Chemoresistance; IGF-1R signaling; Ovarian cancer