Human chorionic gonadotropin (hCG) inhibits cisplatin-induced apoptosis in ovarian cancer cells: possible role of up-regulation of insulin-like growth factor-1 by hCG

Int J Cancer. 1998 May 18;76(4):571-8. doi: 10.1002/(sici)1097-0215(19980518)76:4<571::aid-ijc21>3.0.co;2-9.

Abstract

Gonadotropins have been suggested to play a role in the development or progression of ovarian cancer, and we have previously reported the expression of luteinizing hormone/ human chorionic gonadotropin (LH/hCG) receptor in 40% of epithelial ovarian carcinomas. To examine the biological effect of LH/hCG on ovarian cancer cells, apoptosis induced by cisplatin with or without hCG treatment was investigated in 2 ovarian cancer cell lines, OVCAR-3 and SK-OV-3. Stimulation of cell proliferation by hCG was also studied. In addition, to analyze further the mechanism of hCG signaling involved in apoptosis-inhibition, we examined the expression of LH/hCG receptors and the regulation by hCG for apoptosis-inhibitory pathways, such as the bcl-2/bax system and the insulin-like growth factor-1 (IGF-1)/IGF-1 receptor (IGFR) system. hCG did not increase cell proliferation in either cell line. However, hCG treatment suppressed cisplatin-induced apoptosis by 58% in the OVCAR-3 cells, as shown by immunofluorescent staining and quantitation of DNA fragmentation. LH/hCG receptor mRNA was expressed only in OVCAR-3, and no apoptosis-inhibitory effect of hCG was observed in the SK-OV-3 cells that did not express the receptor. In the OVCAR-3 cells, hCG significantly increased mRNA expression of IGF-1, but did not change mRNA levels of bcl-2/bax. Our findings suggest that LH/hCG influences the chemosensitivity of ovarian cancer cells through an apoptosis-inhibitory signal possibly via up-regulation of IGF-1 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Cell Division / drug effects
  • Chorionic Gonadotropin / pharmacology*
  • Cisplatin / pharmacology*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • RNA, Messenger / analysis
  • Tumor Cells, Cultured
  • Up-Regulation

Substances

  • Chorionic Gonadotropin
  • RNA, Messenger
  • Insulin-Like Growth Factor I
  • Cisplatin