| Objective:To investigate the expression of MDR1,GST-πand p53(Mtp53) in epithelial ovarian carcinoma and the relationship between the expression and the clinical stage,pathological type,chemotherapy resistance,chemotherapy history of epithelial ovarian cancer and to evaluate the role of MDR1,GST-πand p53 on the origin,progression,therapy and prognosis of epithelial ovarian cancer;To study the multidrug-resistant mechanism of ovarian cancer in vitro and to illustruate the relationship between P53 and MDR act as the dependence of choosing clinic therapy, predicting prognosis and finding effective retro-drug- resistance methods.Methods:1. To examine the expression of MDR1,GST-π,p53 in 22 cases of ovarian carcinoma,20 cases of benign ovarian tumor and 18 cases of normal ovarian tissue by SP immunohistochemical technique and reverse transcription polymerase chain reaction(RT-PCR). 2. MTT was used to detect the influence of varied doses and time of cisplatin on the growth of COC1and COC1/DDP cells. Flow cytometry was used to observe the apoptosis of COC1 and COC1/DDP cells. 3. Relative quantitative RT-PCR was used to determine the expression of MDR1,GST-π,p53 mRNA in COC1 and COC1/DDP cells after DDP administered 24 hours.Results:1. In normal ovary,benign tumor and ovarian cancer,the positive of P-gp was 0/18,0/20,9/22,the positive of GST-πprotein was 0/18,0/20,16/22, the positive expression of p53 protein was 0/18,0/20,14/22;in the mRNA level,the positive of MDR1 was 0/18,0/20,12/22, GST-πwas 0/18,3/20,17/22,and p53 was 0/18,0/20,16/22 respectively.The ratios of P-gp,GST-πand p53 expression in ovarian cancer were much higher than that in benign ovarian tumor and normal ovary tissue.The expressions of MDR1 and GST-πwere closely related to non-despendence to chemotherapy.The expression of p53 protein revealed significant relationship to the clinical stage and the histological differentiation.The expression of MDR1 protein was related to the histological differentiation.Significant relationship was found between p53 and MDR1. 2. DDP could inhibit the growth of COC1 and COC1/DDP cells in a time- and dose-dependent fashion. As compared to that of COC1 cells, the apoptosis of COC1/DDP cells was apparently inhibited by DDP with the concentration ranges of 2.5～10μg/mL (P<0.05). 3. RT-PCR showed the expression level of MDR1 and p53 genes in COC1/DDP cells was higher than that in COC1 cells but the expression of GST-лmRNA was no difference. MDR1mRNA was no expression in COC1 cells. The expression of GST-πand p53mRNA was significantly downregulated in a dose-dependent fasion in COC1 cells after DDP administered 24 hours. But there was no significant difference of the expression of MDR1,GST-πand p53mRNA in COC1/DDP cells by DDP.Conclusion:1.The expression of MDR1,GST-πand p53 in ovarian cancer was much higher than that in benign ovarian tumor and normal ovary tissue.Overexpression of MDR1, GST-π, p53 mRNA and their corresponding proteins in epithelial ovarian cancer participated in the formation of multidrug resistance in ovarian cancer and P53 may play a indirected role through regulating the expression of MDR1,GST-π. 2. P53 protein expression related with the histological grade,clinical stages and the malignant degree of ovarian cancer,but not with the histological type.P53 expression could be as a factor both in predicting prognosis of patients and anti-cancer drug resistance in epithelial ovarian cancer.3. The expression of MDR1 and GST-πwas associated with the effectiveness of ovarian carcinoma to chemotherapy. Detection of multidrug resistance related genes in ovarian cancer tissues may be useful to choose drugs. Significant relationship was found between p53 and MDR1. Multi-drug resistance of ovarian cancer is possibly related to apoptosis. 4. DDP could inhibit the growth of COC1 and COC1/DDP cells in a time- and dose-dependent fashion. As compared to that of COC1 cells, the apoptosis of COC1/DDP cells was apparently inhibited by DDP. 5.Inducement of apoptosis is one of the pharmaceutic mechanism of DDP,DDP could induce the apoptosis of COC1 and COC1/DDP cells. Acquired drug resistance is related to apoptosis. 6. The expression level of MDR1 and p53 genes in COC1/DDP cells was higher than that in COC1 cells. The expression of p53mRNA was significantly downregulated in a dose-dependent fasion in COC1 cells by DDP. But there was no significant difference in COC1/DDP cells. Anti-cancer drug resistance of DDP in ovarian cancer is possibly related to inactivation of apoptosis. Multidrug resistance is more common in ovarian cancer. Determination of the expression of MDR1 and GST-πis useful for predicting the sensitivity to chemotherapy. Overexpression of P53(Mtp53) gene may contribute to the decreased susceptibility of cells to apoptosis and the development of multidrug resistance of human ovarian cancer . |
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