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.
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.
Kuroda
H
H
Department of Gynecology and Obstetrics, Faculty of Medicine, Kyoto University, Japan.
Mandai
M
M
Konishi
I
I
Yura
Y
Y
Tsuruta
Y
Y
Hamid
A A
AA
Nanbu
K
K
Matsushita
K
K
Mori
T
T
D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D006063:Chorionic Gonadotropin; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D002945:Cisplatin