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- 2018
TNF-α通过Wnt/β-catenin信号通路促进结肠癌细胞的增殖
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Abstract:
摘要：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。
ABSTRACT: Objective To investigate the effect of treatment with TNF-α on growth ability of colon cancer cells and its possible mechanism. Methods Human colon cancer HT-29 cells were treated with TNF-α (10nmol/L). The effect of TNF-α on the proliferative ability was examined by cell growth curve assay and MTT assay, respectively. Cell cycle was detected by flow cytometry. Protein levels of β-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 of β-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 of β-catenin, c-myc and cyclinD1 (all P<0.05) in the TNF-α-treated HT29 cells. Conclusion TNF-α may 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
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