Dishevelled2在鼻咽癌顺铂耐药中的作用研究?

目的：探讨散乱蛋白2(Dishevelled2,DVL2)对鼻咽癌顺铂化疗敏感性的影响,为进一步研究 DVL2在肿瘤化疗耐药中的作用机制奠定前期基础。方法转染 pcDNA3.1-DVL2至鼻咽癌细胞5-8F,并用不同浓度(0,1,2,4,8,10,20μmol/L)的顺铂处理细胞,MTT 检测过转染 DVL2对5-8F 顺铂抑制率及半数抑制浓度(IC50)的影响,流式检测 DVL2高表达对顺铂的5-8F 细胞凋亡的影响,Western blotting 检测 DVL2对 Wnt/β-catenin 信号的影响。结果过表达 DVL2明显降低了顺铂对5-8F 的抑制率,提高了其 IC50,同时过表达 DVL2明显降低了顺铂诱导的5-8F 细胞的凋亡,进一步研究显示,过表达 DVL2明显增加了β-catenin 及其靶基因 P-gp 和 Survivin 的蛋白表达。结论过表达 DVL2可通过上调 Wnt/β-catenin 信号增强耐药相关蛋白 P-gp、Survivin 的表达,从而诱发鼻咽癌顺铂耐药。

The Role of Dishevelled2 in Cisplatin-based Chemotherapy in Nasopharyngeal Carcinoma

Objective To explore the effect of Dishevelled2 (DVL2 ) on chemotherapy sensitivity of nasopharyngeal carcinoma 5-8F cells to cisplatin,and provide a basis for the research on the mechanism of DVL2 in tumor resistance.Methods The 5-8F cells were transfected by pcDNA3.1-DVL2 and then treated by various concentration of cisplatin.The effects of DVL2 on the cisplatin-mediated inhibition and apoptosis of 5-8F cells were detected by MTT and Flow cytometric assays respectively.The effects of DVL2 on Wnt/β-catenin signaling was examined by Western blotting assay.Results The results showed that the cisplatin-mediated inhibition and apoptosis of 5-8F cells were decreased by overexpression of DVL2,and that the protein levels ofβ-catenin,P-gp and Survivin were increased by overexpression of DVL2.Conclusion The overexpression of DVL2 enhances the resistance of nasopharyngeal carcinoma to cisplatin via upregulation of P-gp and Survivin by Wnt/ β-catenin signaling.