In vitro effects of gonadotropin-releasing hormone (GnRH) analogue on cancer cell sensitivity to cis-platinum.
Six endometrial cancer cell lines (Ishikawa, EIIL, HEC1A, 6, 50 and 59), one breast cancer cell line (MCF-7) and two ovarian cancer cell lines (OVHS-1, HRA) were treated for 24 or 168 h with a gonadotropin-releasing hormone (GnRH) analogue, Buserelin acetate, and the cellular growth profile was studied. All these cell lines except for the HRA line had positive GnRH receptor mRNA expression detected by reverse transcriptase polymerase chain reaction. GnRHa suppressed cell growth after 168 h of exposure, but not after 24 h. Suppression of cell growth by the exposure to cis-platinum (CDDP, 10 nM for 24 h) was significantly increased in the presence of GnRHa for 168 h. The mechanism of this growth inhibition was tested by examining both RNA components of human telomerase (hTR) expression and telomerase activity. The results showed that GnRHa inhibits telomerase activity without altering the RNA component of telomerase expression. The present data suggest that GnRH analogue may modulate endometrial, breast and ovarian cancer cell growth through modifying the telomerase activity. Since GnRHa increased the cytotoxic effects of CDDP and GnRHa is a compound of high patient compliance, the value of GnRHa as a tumor sensitizer to CDDP should be further tested in clinical trials.
Ohta
H
H
Department of Obstetrics and Gynecology, Nihon University School of Medicine, Tokyo, Japan.
Sakamoto
H
H
Satoh
K
K
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002064:Buserelin / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives; D006801:Humans; D012313:RNA / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011966:Receptors, LHRH / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D012313:RNA; D019098:Telomerase; D002064:Buserelin; D002945:Cisplatin