Endocrine Abstracts

Ovarian carcinoma is the most deadly and leading cause of cancer death occurring in the female reproductive tracts. 17β-estradiol (E2) has long been considered as one of the effective causes of ovarian cancer through its actions via estrogen receptors (ERs). In contrast, progesterone (P4) offers protective effect against ovarian carcinogenesis. We predicted that P4 would inhibit the metastasis of BG-1 human epithelial ovarian cancer cells, which was induced by E2. In the present study, we confirmed that E2 increased BG-1 cell viability in a dose-dependent manner, while the effect of E2 was inhibited by the co-treatment of P4. Also we showed that P4 decreased the metastatic potential of BG-1 cells. P4 treatment clearly led to functional changes in cancer cell migratory and invasive propensity. We performed scratch assay and invasion assay to evaluate these functional changes. The results showed that P4 inhibited the migration and invasion activity of BG-1 ovarian cancer cells, which was increased by E2 via its receptor interaction. These alterations were also related with changes in the epithelial-mesenchymal transition (EMT) markers such as E-cadherin, Vimentin, and N-cadherin and EMT-associated transcriptional factors, Snail and Slug, too. Upon P4 stimulation, the expression of the epithelial marker E-cadherin was strikingly increased, whereas the expression of mesenchymal makers like N-cadherin and Vimentin was decreased. EMT-associated transcriptional factors, Snail and Slug, were also significantly down-regulated. These results indicate that P4 can inhibit the migration of BG-1 ovarian cancer cells by reducing EMT. Consequently, the present results represent that P4 is a potent substance which may inhibit the growth of human ovarian cancer cells and metastasis via regulation of PR. Therefore, the hormone therapy using P4 may be a clinically effective tool for the treatment of human epithelial ovarian cancer.