抑制CXCR4基因调控Wnt/β-catenin通路在卵巢癌转移中的作用

Blockage of CXCR4 affects the metastasis of ovarian cancer via Wnt/β-catenin signaling pathway

目的研究趋化因子受体4(chemokine receptor 4,CXCR4)在卵巢癌转移中的作用及其机制。方法采用Real-time PCR和Western blot法检测正常卵巢组织、卵巢癌组织和卵巢癌细胞株(CAOV3)CXCR4mRNA和蛋白的表达以及CXCR4shRNA转染后卵巢癌CAOV3中CXCR4mRNA和蛋白的表达;MTT法检测CXCR4shRNA对卵巢癌细胞增殖的影响;通过Transwell侵袭实验检测CXCR4基因沉默对卵巢癌细胞侵袭性的作用;Real-time PCR法检测CXCR4shRNA转染后Wnt/β-catenin通路相关基因和EMT相关基因的mRNA表达。结果 CXCR4在卵巢癌组织和CAOV3细胞中的表达明显高于正常卵巢组织;转染CXCR4shRNA可有效抑制CAOV3细胞中CXCR4mRNA和蛋白表达;CXCR4基因沉默可有效抑制细胞增殖、降低细胞侵袭性;同时明显抑制Wnt/β-catenin通路相关基因CTNNBI、C-MYC、MMP-9和CD44以及EMT相关基因SLUG和Vimentin的mRNA表达。结论 CXCR4通过调控Wnt/β-catenin通路影响卵巢癌的转移。

Objective To determine the role and the possible mechanisms of chemokine receptor 4（CXCR4）in the metastasis of ovarian cancer.Methods Real-time PCR and Western blot were used to analyze the expression of CXCR4 in normal ovarian tissues,malignant epithelial ovarian tumors and ovarian cancer cell lines and the expression of CXCR4 in CAOV3 cell after transfected with shRNA against CXCR4.MTT assay and Transwell migration assay were used to detect the resulting alterations in cell proliferation and migration.Last,we detected the mRNA expression of Wnt/β-catenin related genes and EMT-related genes.Results CXCR4 was highly expressed in malignant ovarian tumors and ovarian cancer cell lines.CXCR4 expression was inhibited by shRNA against CXCR4.Knockdown of CXCR4 could obviously reduce the proliferation and invasion of ovarian cancer cells.Moreover,Wnt target genes（CTNNBI,C-MYC,MMP-9,and CD44）and mesenchymal markers such as Vimentin and SLUG were also inhibited by shRNA against CXCR4.Conclusion CXCR4 plays a critical role in the metastasis of human ovarian cancer through modulating the Wnt/β-catenin signaling pathway.