Wnt/β-catenin/TCF-4通路对肾癌细胞生物学行为的影响及其机制  

The role of Wnt/β-catenin/TCF-4 pathway on biological behavior of renal cell carcinoma and its mechanism

作　　者：陈少安 苏增存 陈友根 夏庆华[1] 邢念增 Chen Shaoan;Su Zengcun;Chen Yougen;Xia Qinghua;Xing Nianzeng(Department of Urology,Shandong Provincial Hospital,Jinan 250021,China;Department of Ultrasound,Shandong Provincial Hospital,Jinan 250021,China;Department of Urology,Cancer Hospital,Chinese Academy of Medical Sciences,Beijing 100021,China)

机构地区：[1]山东省立医院泌尿外科,济南250021 [2]山东省立医院超声科,济南250021 [3]中国医学科学院肿瘤医院泌尿外科,北京100021

出　　处：《中华医学杂志》2020年第24期1890-1894,共5页National Medical Journal of China

基　　金：山东省自然科学基金(ZR2017PH038)。

摘　　要：目的探讨Wnt/β-连环链蛋白(catenin)/TCF-4通路在肾癌细胞中的作用,并初步分析其可能的机制。方法分别构建β-catenin sh和TCF-4△Nsh的真核表达载体,并分别转染肾癌786-O细胞,采用CCK8检测转染后细胞的增殖能力,吖啶橙-溴乙锭(AO-EB)染色法检测转染后细胞死亡情况,Western印迹检测转染组、空转组以及空白组细胞TCF-4、Bcl-2、bax、Caspase-3的表达情况。结果转染β-catenin siRNA病毒后,细胞的增殖能力较空转组明显降低(0.443±0.145与0.910±0.721),细胞死亡率较空转组明显增加(16.38±5.32与6.61±1.04),TCF-4的表达受抑制、凋亡蛋白Caspase 3、bax表达增加、抗凋亡蛋白Bcl-2表达减低(均P<0.05)。转染TCF-4 siRNA病毒后,细胞的增殖能力较对照组明显降低,细胞死亡率较对照组明显增加,TCF-4的表达受抑制导致凋亡蛋白Caspase 3、bax表达增加,抗凋亡蛋白Bcl-2表达减低(均P<0.05)。结论Wnt/β-catenin/TCF-4通路在786-O肾癌细胞中具有可调节肾癌细胞的增殖和凋亡的作用,其机制可能为通过调节其下游的凋亡蛋白Caspase 3、bax和抗凋亡蛋白Bcl-2的表达水平来实现。Objective To investigate the role of Wnt/β-catenin/TCF-4 pathway in renal cancer cells and to analyze its possible mechanism.Methodsβ-catenin and TCF-4 were inhibited by siRNA in 786-O cells.The proliferation of transfected cells was detected by CCK8.The cell death of transfected cells was detected by acridine orange-ethidium bromide staining.The expressions of TCF-4,bcl-2,bax and Caspase-3 were detected in transfection group,empty vector group and negative control groups by western blot.Results The cell proliferation ability of theβ-catenin transfection group was significantly lower than that of the control group(0.443±0.145 vs 0.910±0.721),meanwhile,the cell death rate was significantly increased(16.38±5.32 vs 6.61±1.04),the expression level of Caspase 3 and bax was increased,and the expression of anti-apoptotic protein Bcl-2 was decreased.Decreased TCF-4 led to the same results as inhibition ofβ-catenin(all P<0.05).Conclusion The Wnt/β-catenin/TCF-4 pathway may play a role in the regulation of proliferation and apoptosis in 786-O renal cancer cells.The mechanism might through regulating of the downstream apoptosis proteins Caspase 3,bax and anti-apoptotic protein Bcl-2.

关 键 词：肾肿瘤 Wnt/β-catenin/TCF-4信号通路 786-O肾癌细胞 增殖 凋亡 

分 类 号：R737.11[医药卫生—肿瘤]