Anti-angiogenic effect of medroxyprogesterone acetate therapy on ovarian cancer in vivo

Objective To investigate the inhibitory effects of medroxyprogesterone acetate (MPA) on an-giogenesis and growth of ovarian cancer cells in nude mice. Methods Ovarian cancer cells of line COC1 originated from human ovarian serous adenocarcinoma were implanted in nude mice. Three groups were set up: two study group (MPA in different dosages) and a control group. Each group included ten nude mice. MPA was administered sc at the dose of 60 mg/kg and 120 mg/kg, respectively in two study groups 2 times/w for four weeks. Six weeks after implantation, the weight of nude mice was observed and the morphology of tumor cells was observed with electronmi-croscope. The microvascular density ( MVD) was examined by immunohistochemical staining with anti-human factor Ⅷ antibody.Results Compared with the control,the tumor growth inhibitory rate in the study group was 23.8% and 43.8% at the dosage of 60 mg/kg and 120 mg/kg, respectively. MVD was decreased in study groups of 60 mg/ kg and 120 mg/kg(3.64±0.02,2.11±0.12)as compared with that (5.14±0.74) in control group(P 0.05, P 0.01, respectively) , and was different significantly between the two study groups( P 0.01). Many morphological characteristics including compactness and margination of nuclear chromatin, apoptotic bodies , and necrosis of cells increased significantly in the study groups. Conclusion It was suggested from the present study that MPA can inhibit the angiogenesis and growth of ovarian cancer cells in nude mice, which presents dose-response relationship. Its anticancer effect seems to be due to induction of apoptosis which may be a result of anti-angiogenesis rather than direct anti-cancer cell effect.