Abstract:
Objective To examine hMSH2 expression in ovarian epithelial cancer tissues with different chemosensitivity, and to investigate the association between hMSH2 expression and chemoresistance. Methods Tissues were collected from 80 patients who underwent cytoreductive surgery. Viable ovarian cancer cells obtained from malignant tissues were tested for the sensitivity to paclitaxel, carboplatin, topotecan, gemcitabine, docetaxel, etoposide, bleomycin and 4-hydroperoxycyclophosphamide using ATP-TCA. The expression levels of hMSH2 mRNA and protein in 80 cases of ovarian carcer tissues were determined by real-time PCR and Western blot assay. Results There were significant differences of hMSH2 mRNA and protein expression in epithelial ovarian cancer tissues. The resistance to paclitaxel group showed higher hMSH2 expression at both mRNA and protein levels than the sensitive one (
P<0.01). The same results were detected in carboplatin, docetaxel and topotecan groups(P<0.05). The expression levels of hMSH2 were correlated with the sensitivity indexes to docetaxel, topotecan and carboplatin (
P≤0.05). The early-stage (Ⅰ, Ⅱ) ovarian epithelial cancer tissues showed lower hMSH2 expression than advanced-stage (Ⅲ) ones(
P<0.05). The well- to morderate-differentiated ovarian epithelial cancer tissues showed lower hMSH2 expression at protein levels than the poor-differentiated ones (
P=0.000). Primary ovarian epithelial cancer tissues showed lower hMSH2 expression than the recurrent ones (
P<0.01). Conclusion hMSH2 overexpression is correlated to chemotherapy resistance and poor prognosis of ovarian cancer. Chemotherapy could induce high expression of hMSH2. Down-regulating hMSH2 expression may be a new method in ovarian cancer therapy.