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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
Author(s) -
Kuroda Hideki,
Mandai Masaki,
Konishi Ikuo,
Yura Yasuichiro,
Tsuruta Yuko,
Hamid Atia A.,
Nanbu Kanako,
Matsushita Katsuko,
Mori Takahide
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980518)76:4<571::aid-ijc21>3.0.co;2-9
Subject(s) - human chorionic gonadotropin , endocrinology , apoptosis , medicine , gonadotropin , biology , ovarian cancer , receptor , cisplatin , cancer cell , luteinizing hormone , hormone , cancer , chemotherapy , biochemistry
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. Int. J. Cancer 76:571–578, 1998.© 1998 Wiley‐Liss, Inc.