卵巢上皮癌组织中hMSH2的表达及其与化疗耐药的关系

目的 检测不同化疗敏感程度的卵巢上皮癌组织中hMSH2基因的表达，分析其与化疗耐药及预后的关系。方法 80例新鲜卵巢上皮癌组织均由手术中取得，采用ATP-TCA技术检测卵巢癌组织对八种药物：紫杉醇、卡铂、拓泊替康、多西他赛、吉西他滨、环磷酰胺体内代谢产物、依托泊苷及博来霉素的体外敏感性。采用Real-time PCR及Western blot法分别检测80例卵巢上皮癌组织中hMSH2 基因mRNA和蛋白水平的表达情况。结果 对紫杉醇耐药的卵巢上皮癌组中，hMSH2基因在mRNA及蛋白水平的表达均明显高于敏感组（P<0.01），在对卡铂、拓泊替康、多西他赛耐药组中hMSH2表达水平也明显高于敏感组（P<0.05）；hMSH2基因的相对表达值与卡铂、拓泊替康、多西他赛的敏感度系数有显著相关性（P≤0.05）。早期卵巢癌患者组织的hMSH2表达水平明显低于晚期卵巢癌组织（P<0.05）。高、中分化卵巢癌组织hMSH2蛋白表达水平明显低于低分化卵巢癌组织（P=0.000）。原发卵巢癌患者组织的hMSH2表达水平明显低于复发卵巢癌患者组织（P<0.01）。结论 hMSH2基因的高表达与卵巢癌化疗耐药及预后相关，化疗可能诱导hMSH2基因的高表达；下调hMSH2基因的表达或许是逆转肿瘤耐药的新途径。

hMSH2 Expression in Ovarian Epithelial Cancer Tissues and Its Relationship with Chemoresistance

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.