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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.
AuthorsRam K Singh, Snehal M Gaikwad, Ankit Jinager, Smrita Chaudhury, Amita Maheshwari, Pritha Ray
JournalCancer letters (Cancer Lett) Vol. 354 Issue 2 Pg. 254-62 (Nov 28 2014) ISSN: 1872-7980 [Electronic] Ireland
PMID25157649 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Chemical References
  • picropodophyllin
  • Receptor, IGF Type 1
  • Proteasome Endopeptidase Complex
  • Podophyllotoxin
  • Paclitaxel
  • Cisplatin
Topics
  • Antineoplastic Combined Chemotherapy Protocols (pharmacology)
  • Carcinoma, Ovarian Epithelial
  • Cell Line, Tumor
  • Cisplatin (administration & dosage, pharmacology)
  • Down-Regulation
  • Drug Resistance, Neoplasm
  • Drug Synergism
  • Female
  • Humans
  • Molecular Targeted Therapy
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial (drug therapy, metabolism, pathology)
  • Ovarian Neoplasms (drug therapy, metabolism, pathology)
  • Paclitaxel (administration & dosage, pharmacology)
  • Podophyllotoxin (administration & dosage, analogs & derivatives, pharmacology)
  • Proteasome Endopeptidase Complex (metabolism)
  • Receptor, IGF Type 1 (antagonists & inhibitors, biosynthesis)

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