Assay For Drug Resistance-Associated Protein Expression In Epithelial Ovarian Cancer And Study On The Role Of Mbfepristone In Promoting Sensitivity Of Skov3to Cisplatin

Objective:To investigate the expression of drug resistance-associated proteins in ovarian cancer, and to evaluate whether mifepristone could promote the sensitivity of ovarian cancer cell SKOV3to cisplatin.Method:1The expression of IGF-IR, ANNEXINA3and MDr-lwas detected by immunohistochemical staining in blocks of78cases with ovarian cancer, to analyze their association with histological types..differentiation, and thus in survival.2To explore the effect of mifipristone upon sensitivity of ovarian cancer cells to cisplatin, cell proliferation of SKOV3was assessed by MTT assay after exposed to mifepristone; single cell gel electrophoresis assay (comet assay) was performed to detect the apoptosis of SKOV3cells treated by cisplatin with mifipristone combined or not; finally, the expression of IGF-IR, ANNEXINA3,MDr-1in SKOV3cells was measured by Western blot after treated with mifepristone Result:1. Three kinds of drug resistence-related proteins (IGF-IR, ANNEXINA3and MDr-1) present with different expression level among patients with different histological types and differentiation, and their expression level was found to be inversely related with survival.2. Mifepristone inhibited ovarian cancer cell proliferation at low concentrations, and killed the cells at high concentrations as shown in MTT assay. The number of apoptotic cells were increased significantly when exposed to low concentrations of mifepristone combined with cisplatin as compared with those treated with cisplatin alone (p<0.05).3. Comet assay showed that compared with control, the number of apoptotic cells was increased significantly when exposed to Mifepristone with cisplatin (p<0.05)4. The expressions of IGF-IR and MDr-1in the SKOV3cells could be induced by cisplatin. However, mifepristone exposure could decrease such induction.Conclusion:Epithelial ovarian cancer holds different expression level of Cisplatin resistance-associated proteins with different histologic types and differentiation. Mifepristone itself could induce the apoptosis of ovarian cancer cell SKOV3. Moreover, it could promote the apoptosis effect induced by cisplatin through down regulating the expressions of IGF-IR, MDr-1in the SKOV3cells.