Basic and Clinical study of hormonal (GnRHa) treatment for ovarian cancer

Research Project

Project/Area Number	07671829
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Obstetrics and gynecology
Research Institution	Nihon University
Principal Investigator	TANAKA Hitoshi (1996) Nihon University, School of Medicine, Obstetrics and Gynecology, Assistant, 医学部, 助手 (10256860) 斉藤綾子 (1995) 日本大学, 医学部, 助手 (90246885)
Co-Investigator(Kenkyū-buntansha)	SAKAMOTO Hideki Nihon University School of Medicine, 医学部, 助教授 (80158922) SATOH Kazuo Nihon University School of Medicine, 医学部, 教授 (80010180) 高見雅司日本大学, 医学部, 助手 (80256859)
Project Period (FY)	1995 – 1996
Project Status	Completed (Fiscal Year 1996)
Budget Amount *help	¥1,900,000 (Direct Cost: ¥1,900,000) Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000) Fiscal Year 1995: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywords	ovarian cancer / GnRHa / growth / invasion / telomerase / adjuvant therapy / Ovarian cancer / gonadotropir releasing horncove / ovarian cancer / gonadotropin releasing hormone
Research Abstract	In this study, we examined the effect of gonadotropin releasing hormone agonist (GnRHa) on cell growth, invasion and metastasis of epithelial ovarian cancer cells. GnRHa inhibited the growth of several epithelial ovarian cancer cell lines, including chemotherapy-resistant clear cell carcinoma, which possessed GnRH receptor and telomerase activity. GnRHa also inhibited telomerase activity resulting in shorter extension of telomerase, whereas GnRHa showed no inhibition on growth and telomerase activity of an ovarian cancer cell line lacking GnRH receptor. In addition, GnRHa induced M1 senescence of GnRH receptor positive cancer cells. Moreover GnRHa inhibited the penetrating ability of ovarian cancer cells through Matrigel membrane in invitro invasion assay. These results suggest that GnRHa may not only alter immortality or induce cell crisis but also inhibit the invasion through a GnRH receptor mediated mechanism in epithelial ovarian cancer cells. Based on these results, GnRHa has been used as a adjuvant therapy for 3 patients bearing advanced epithelial ovarian cancers (IIIc ; 2, IV ; 1) with the informed consent and revealed no change of disease for 12-26 months.