HNF4A对结直肠癌细胞增殖的影响及其机制

Effect of HNF4A on Proliferation of Colorectal Cancer Cells and Its Mechanism

目的明确HNF4A在结直肠癌发生发展中的作用及机制,探究HNF4A作为结直肠癌治疗新靶点的理论依据。方法收集117例结直肠癌患者的临床资料,分析HNF4A的表达与患者临床病理特征的关系。成功构建高、低表达HNF4A的结直肠癌细胞系(LoVo、SW620、HT-29、SW480),通过BrdU实验和MTT实验检测HNF4A对细胞增殖的影响;通过Western blot检测高、低表达HNF4A后p53及p21的蛋白表达变化。结果淋巴结转移患者中高表达HNF4A的比例明显减少(P<0.05);肿瘤分期越晚,高表达HNF4A的患者比例越低(P<0.05)。高表达HNF4A的LoVo、SW620细胞增殖能力明显受到抑制(均P<0.01);低表达HNF4A的HT-29、SW480细胞增殖能力明显提高(均P<0.01)。高表达HNF4A可以诱导p53和p21表达;反之,低表达HNF4A则抑制p53、p21的表达。结论HNF4A在结直肠癌发生发展中起到重要作用,其机制可能是影响p53/p21信号通路。

Objective To determine the role and possible mechanism of HNF4 A in the development of colorectal cancer,and to explore the theoretical basis of HNF4 A as a new target for the treatment of colorectal cancer.Methods Totally,117 patients with colorectal cancer were collected,and the relationship between the expression level of HNF4 A and clinical characteristics of colorectal cancer was analyzed.Colorectal cancer cell lines(LoVo,SW620,HT-29 and SW480)with high and low expression of HNF4 A were successfully constructed,and the effect of HNF4 A on proliferation of colorectal cancer cells was detected by BrdU assay.The effect of HNF4 A on cell proliferation was further verified by MTT assay.The expression levels of p53 and p21 were detected by Western blotting after high and low expression of HNF4 A.Results The proportion of patients with high expression of HNF4 A was significantly decreased in patients with lymph node metastasis(P<0.05).The later the tumor stage,the lower the proportion of patients with high expression of HNF4 A(P<0.05).As compared with the negative control group,the proliferation of highly expressed HNF4 A cells was significantly inhibited(P<0.01).Compared with the negative control group,the proliferation of cells with HNF4 A knock-down was significantly enhanced(P<0.01).High expression of HNF4 A could up-regulate the expression of p53 and p21.Conversely,the low expression of HNF4 A inhibited the expression of p53 and p21.Conclusion HNF4 A may play an important role in the development of colorectal cancers,possibly by regulating the p53/p21 signaling pathway.