DHRS2蛋白对结直肠癌细胞化疗敏感性的影响

Effect of DHRS2 protein on chemosensitivity of colorectal cancer cells

目的研究DHRS2蛋白对肠癌耐药细胞敏感性影响及其机制。方法利用串联质谱标签法(TMT)对结直肠癌耐药细胞系HCT116/OXA与其亲本进行差异蛋白筛选;CCK-C法检测结直肠癌耐药细胞株HCT116/OXA对奥沙利钳敏感性及沉默DHRS2蛋白对其耐药性影响;蛋白质印迹法验证差异表达蛋白以及检测沉默DHRS2蛋白后对相关信号通路蛋白调节作用。结果耐药细胞株HCT116/OXA中DHRS2蛋白水平明显高于亲本细胞株(P<0.001);沉默DHRS2蛋白可增加HCT116/OXA对奥沙利钳的敏感性;同时下调P53蛋白和切除修复交叉互补基1(ERCC1)蛋白的表达。此外,干扰P53蛋白后,ERCC1蛋白表达也明显减少。结论沉默DHRS2蛋白可部分恢复结直肠癌耐药细胞株HCT116/OXA对化疗药物敏感性,其机制可能为通过下调P53蛋白进而抑制ERCC1蛋白表达引起。

Objective To investigate the influence of dehydrogenase/reductase SDR family member 2(DHRS2)on chemosensitivity of colorectal cancer cells.Methods Differentially expressed proteins in the HCT116 and HCT116/0XA cell lines were performed by using tandem mass tag(TMT).The sensibility of HCT116 cells and HCT116/0XA cells to oxaliplatin(OXA)and the effect of DHRS2 on sensibility of HCT116/0XA cells to oxali-platin were measured by CCK-8 assay.The protein expression of DHRS2,p53 and ERCC1 were detected by West-ern blot.Results Compared to HCT116 cells,the expression of DHRS2 in HCT116/0XA was significantly in-creased.CCK-8 assay revealed that silencing of DHRS2 sensitizes HCT116/OXA to oxaliplatin.The results of W estern blot demonstrated that knockdown DHRS2 could regulate ERCC1 to increase chemotherapy resistance by a p53-dependent pathway.Conclusion Silencing DHRS2 in HCT116/0XA efctively restores OXA-sensitivity through suppressing the expression of ERCC1 via a p53-dependent pathway.