TNF-α通过Wnt/β-catenin信号通路促进结肠癌细胞的增殖

TNF-αpromotes the proliferation of colon cancer cells by activating the Wnt/β-catenin pathway

目的探讨TNF-α对结肠癌细胞增殖的影响,并初步探讨其分子机制。方法用生长曲线实验和MTT法检测TNF-α(10nmol/L)对结肠癌细胞HT-29增殖的影响;流式细胞仪检测TNF-α对结肠癌细胞周期的影响;Western blot检测TNF-α对β-catenin、c-myc及cyclinD1的影响;观察XAV939阻断Wnt/β-catenin信号通路对TNF-α促进结肠癌细胞增殖及Wnt/β-catenin信号通路相关蛋白的影响。结果 TNF-α(10nmol/L)组结肠癌细胞HT-29增殖明显增快(P均<0.05),G0/G1期细胞明显减少(P<0.05),S期细胞明显增多(P<0.05),G2/M期细胞比例没有统计学差异(P>0.05)。TNF-α可促进结肠癌细胞中β-catenin、c-myc及cyclinD1蛋白的表达(P均<0.05);XAV939减弱了TNF-α对结肠癌细胞增殖的作用(P均<0.05),而且β-catenin、c-myc及cyclinD1的蛋白表达降低(P均<0.05)。结论 TNF-α可能通过激活Wnt/β-catenin信号通路促进结肠癌细胞的增殖,从而参与结肠癌的发生发展。

Objective To investigate the effect of treatment with TNF-αon growth ability of colon cancer cells and its possible mechanism.Methods Human colon cancer HT-29 cells were treated with TNF-α（10 nmol/L）.The effect of TNF-αon the proliferative ability was examined by cell growth curve assay and MTT assay,respectively.Cell cycle was detected by flow cytometry.Protein levels ofβ-catenin,c-myc and cyclinD1 were detected by Western blot.We also observed the effect of the Wnt/β-catenin pathway blockage by XAV939 on TNF-α＇s promoting proliferation of colon cancer cells and proteins related to the Wnt/β-catenin pathway.Results Upon treatment with TNF-α,the proliferative ability of HT-29 cells was enhanced（all P〈0.05）,G0/G1 phase cell ratio was decreased（P〈0.05）,and S phase cell ratio was increased（P〈0.05）.The protein levels ofβ-catenin,c-myc and cyclinD1 were increased in TNF-α-treated HT-29 cells（all P〈0.05）.XAV939 treatment resulted in a significant inhibition of cell proliferation ability（all P〈0.05）as well as the protein levels ofβ-catenin,c-myc and cyclinD1（all P〈0.05）in the TNF-α-treated HT29 cells.Conclusion TNF-αmay be involved in the occurrence and development of colon cancer by activating the Wnt/β-catenin pathway and promoting the proliferation of colon cancer cells.