Effect of Estradiol Combined with Progestogen on Apoptosis of Ovarian Cancer Cell and Expression of MicroRNA-15a

OBJECTIVE To evaluate the effect of estradiol(E2) combined with progestogen(P4) on expression of microRNA-15a(miR-15a). METHODS The primary ovarian cancer cells from clinical ovarian cancer tissues were isolated and cultured, and divided into 3 groups:E2 group, P4 group, E2 combined with P4(E2+P4) group. The survival rate of ovarian cancer cells after the treatment was analyzed by MTT assay. Apoptosis rate and cell cycle were measured by flow cytometry. Moreover, the relative abundance of miR-15a, Bcl-2 and Bax expressions were detected by qRT-PCR. RESULTS High concentration (10^-4 mol·L^-1) of E2, P4 and E2+P4 inhibited the survival rate of ovarian cancer cells with a time dependent manner. However, low concentration(≤ 10^-8 mol·L^-1) of E2 induced the survival rate of ovarian cancer cells. Compared with control group, high concentration of E2, P4 and E2+P4 induced apoptosis of ovarian cancer cells(P<0.001), and the most obvious effect of promoting apoptosis was E2+P4. However, low concentration of E2 reduced apoptosis of ovarian cancer cells(P<0.001). E2, P4 and E2+P4 had no effect on cell cycle. High concentration of E2, P4 and E2+P4 reduced the expression of Bcl-2(P<0.05 or P<0.001), but they induced the expression of Bax(P<0.001). However, the effect of low concentration of E2 was opposite. Moreover, high concentration of E2+P4 could promote the expression of miR-15a(P<0.001). CONCLUSION High concentration of E2, P4 and E2+P4 significantly inhibit the survival and promot the apoptosis, reduce the expression of Bcl-2, and induce the expression of Bax in ovarian cancer cells. However, the effect of low concentration of E2 is opposite. High concentration of E2+P4 can induce the expression of miR-15a.