Relatioship Between FSH And Heterotransplanted Epithelial Ovarian Cancer In Nude Mice Model

【Objective】Ovarian cancer is the most lethal gynecological malignant tumor, although only accounts for 3% of all malignant tumors, but still keep a high mortality rate in the whole world. The incidence of ovarian cancer was higher in 56 to 60 years old, especially the epithelial ovarian cancer (EOC) which composed about 90% of all cancers. And the majority of women have been diagnosed in late stage of the diseases, so although there are much more progress in surgery as well as in chemotherapy on EOC, but the 5-year survival rate is still lower, just in a 30%～40%. Therefore, we need to continue to search the etiology and relevant factors about the EOC. And try to prevention EOC.There are a lot of epidemic data shows that Chinese incidence of EOC is 23% in 75 years old women, which is higher than in American. And it also shows that the incidence is lower in population of having one more children as well as undertaking oral contraceptives. As we know that most Chinese women only has one child; and usually put on IUD for contraception. So it indicated that Chinese women have more chance exposing the high level of FSH situation. Is there any passive relationship?In recent 20 years, there were a lot of in vitro studies showed that FSH could promote ovarian cancer cell proliferation, inhibit apoptosis, promote cells invading growth and VEGF expression, but seldom in vivo experiments, and gave us a direct promote proliferation role, only showed FSH and LH induce tumor angiogenesis, and promote VEGF could expression which also appeared a dose-response effect. So a considerable in vivo study may be contributing a further in formation to help us to understanding the etiology of EOC.【Method】Took HO8910 which was poorly differentiated adenocarcinoma of ovarian cell lines cultured with 10% bovine fetal serum RPMI 1640 medium, for several generations, and then implanted which 0.2ml HO8910 cell contained 5×108/L into the subcutaneous tissue in 15 female nude mice. The 15 nude mice aged from 4～6 weeks, weighted 19～22g,could be divided randomly into 3 groups. Each group contain 5 nude mice, and give intraperitoneal injection of saline 0.1 ml/d, low dose FSH 3IU/d, high dose FSH 10IU/d, for 42 days respectively. Every three days measuring the tumor size by the vernier caliper, and the drawing the growth curve, also observing the general state as well as body weight changes. After 42 days, excise nude mice left eye ball for collection serum. Remove subcutaneous transplant tumor for weighing and section staining on the expression of tumor tissue. Through the immunehistochemical method and measuring the expression of the formation of blood vessels related factors, cell growth stimulating factor receptor. Experimental results were analyzed using statistical software SPSS 13.0 processing, tumor growth curve applied t-test, immunohistochemical results employed by using variance analysis for differences (P < 0.05) with a statistical significance.【Results】1. The serum FSH level elevated in both experimental groups, and high up the menopausal stage.2. The subcutaneous transplant tumor volume and quality was significantly greater high doses FSH group of nude mice than that of in normal control groups and low dose FSH group, it also greater in low-dose FSH group nude mice than in normal control groups (P < 0.05). But there was no significant difference or nude mice body weight in the three groups.3. FSHR expression are all positive, in three groups, and high FSH,level with high FSHR expression.4. There were rich expressions of VEGF in and distributed from tumor cells, mesenchymal cells, multinucleated giant cells and endothelial cells. It also expressed obviously higher in high doses FSH group than that of the other two groups, also higher in low doses FSH group than in that of control group (P < 0.05). 【Conclusion】The present result shows that there is a close relationship between FSH ovarian cancer as well as its development with oncology. FSH can promote the growth of ovarian cancer transplant tumors, and there is a close dependant effects. Meanwhile FSH increases the VEGF expression in the transplanted ovarian tumors indirectly.