The Effect Of Estrogen Or Progesterone Combined Paclitaxel On Human Ovarian Cancer Cell Growth And Drosha Expression

Purpose:To investigate the effect of Estrogen(E2),Progesterone(P4),Paclitaxel(Taxol) on the growth of cells in primary human ovarian cancer cell in vitro and to explore the mechanism of the drugs. To provide a theoretical clues for the pre-clinical treatments of ovarian cancer.Methods:The groups consisted of phase concentration of paclitaxel act on human ovarian cancer cells in vitro. The inhibition rate of ovarian cancer cell after the treatment of Paclitaxel with24h,48h,72h was assessed by methyl thiazolyl tetrazolium (MTT) assay.According to the IC50select the following experimental drug concentration. According to the result of pre-investigation, the10-4mol/L of estrogen could inhibite proliferation of ovarian cancer cells. Categories were set to the control group, E2group, P4group,Taxol group,E2+Taxol group,P4+Taxol group.The ovarian cancer cells were intervented of drugs with48h. Cell apoptosis rate and cell cycle were measured by FACS analysis.The relative abundence of drosha expression was detected by real-time quantitative PCR (qRT-PCR) and Western blotting.Results:①MTT:Estrogen(10-4mol/L), Progesterone(10-4mol/L),Paclitaxel(10ug/ml), E2+Taxol group,P4+Taxol group could inhibit the proliferation of human ovarian cancer cells and induce inhibition rate; E2could induced the inhibition rate of ovarian cancer. Inhibition rate was higher in cells which estrogen receptor (-) than the estrogen receptor (+)(P <0.05). E2+Taxol had significantly inhibition rate in ovarian cancer cells. P4could increase the inhibition rate of ovarian cancer (P<0.05).②FACS to detect apoptosis:Paclitaxel can increase the apoptosis rate of ovarian cancer cell,It had significantly difference compared with the control group (P<0.05). E2+Taxol significantly induced the apoptosis rate of ovarian cancer cells. Progesterone and P4+Taxol also induced apoptosis (P<0.05).①FACS to detect the cell cycle:a large number of cells was arrested in S phase after E2treatment. A large number of cells was arrested in G2/M phase after taxol treatment. Paclitaxel can raise the expression of drosha gene and protein (P<0.001).④The influence of estrogen to drosha gene and protein associated with estrogen receptor in ovarian cancer cells. ER (-),expression of drosha gene and protein was induced (P<0.001), but it has no significate effect in ovarian cancer which estrogen receptor (+).E2+Taxol could increase the expression of drosha, which was higher than the control group (P<0.001). Progesterone group and P4+Taxol could raise the expression of drosha gene and protein (P<0.001), but the effect of P4+Taxol had no statistically difference cpmpared with the effect of paclitaxel.Conclusion:Estrogen, progesterone,paclitaxel could inhibit the growth of human ovarian cancer cells in vitro culture, the three kinds of drugs could change the cell apoptosis rate, estrogen and taxol could change the cell cycle. Estrogen, progesterone combined with paclitaxel by raising drosha expression acted as tumor suppressor or sensitization effect, and it is associated with the expression of estrogen receptor.