Abstract:
Objective To assess the role of TopoⅡα,GST-π and P-gp in drug-resistance of ovarian cancer and their value as predictors of chemotherapeutic response and prognosis. Methods The expression of GST-π,P-gp and TopoⅡ α in the surgical specimens were detected by immunohistochemistry and their relationship with the chemotherapeutic response and prognosis of the patients were analyzed.The expression of GST-π and MDR-1/P-gp in human ovarian cancer cells was silenced by RNA:to evaluate the feasibility of reversal MDR phenotype in the cells. ResultsChemotherapeutic response was no difference with negative TopoⅡα and positive.Chemotherapeutic response was more favorable in patients with negative GST-π than in those with positive expression (
P=0.009).Similar trend occurred with P-gp,though the difference was not significant (
P=0.059).Although log-rank test showed a longer survival in patients with negative GST-π or P-gp (
P=0.012;
P=0.000),Cox hazard analysis did not indicate they could be regarded as prognostic predictors (
P=0.682;
P=0.101).However,when their co-expression status was taken into account,it was found that 100.0% patients with co-negative GST-π/P-gp responded well to chemotherapy and 85.7% patients were still alive until the evaluation.Co-negative GST-π /P-gp presented better chemotherapeutic response and prognosis (
P=0.001;
P=0.000).Furthermore,decreased drug sensitivity accompanied with overexpressed GST-π and P-gp level was found in MDR ovarian cancer cell lines. Conclusion GST-π and P-gp are involved in the forming of MDR in ovarian cancer.The reliability of MDR-1 and GST-π alone as indicators of chemotherapeutic response and prognosis is limited,and co-detection of their expression may provide a higher predictive value. After silencing the expression of GST-π and P-gp by RNAi,the drug sensitivity of the MDR cells were increased.