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机构地区:[1]重庆医科大学病原生物学教研室,400016 [2]重庆医科大学临床检验诊断学实验室
出 处:《中华肿瘤杂志》2007年第5期325-328,共4页Chinese Journal of Oncology
基 金:重庆市教委科研项目(040308)
摘 要:目的探讨双歧杆菌脂磷壁酸(LTA)对结肠上皮细胞癌LoVo细胞内凋亡抑制因子survivin表达的影响及其调控机制。方法采用RT-PCR和Western blot方法分别检测经双歧杆菌LTA处理后LoVo细胞中survivin mRNA和survivin蛋白表达的变化;用Western blot检测PI3K/AKT细胞信号通路中关键蛋白激酶AKT的磷酸化型pAKT(Thr308)以及p53和PFEN表达的变化。结果结肠癌LoVo细胞中存在survivin mRNA和蛋白的高表达,经LTA处理后其表达水平均明显下降(P〈0.01);AKT蛋白激酶活性在LTA处理后也明显降低(P〈0.01);而与下调survivin蛋白相关的p53和PTEN表达上升(P〈0.01),且呈现一定的剂量依赖性。结论双歧杆菌LTA可以通过抑制PI3K/AKT细胞信号通路的活性,促进p53的表达,抑制凋亡抑制蛋白survivin的活性,导致caspases酶活性升高,诱导了LoVo细胞凋亡的发生。Objective The aim of this study is designed to explore the anti-tumor effect of lipoteichoic acid(LTA)of Bifidobacterium on the expression of survivin in colon cancer LoVo cells and its possible regulatory mechanism. Methods The changes of survivin mRNA and protein in LoVo ceils treated with LTA of Bifidobacterium were detected by RT-PCR and Western blot. Meanwhile, the expressions of pAKT(the key protein kinase in PI3K/AKT signal transduction pathway), p53 and PTEN were measured by Western blot. Results There were overexpressions of survivin mRNA and protein in LoVo cells. After treated with different dose of LTA of Bifidobacterium, the expressions of survivin mRNA and protein were markedly decreased in a dose-dependent manner( P 〈 0.01 ). Besides, the activity of pAKT was decreased significantly( P 〈 0.01 ) and the expression of p53 and PTEN was increased ( P 〈 0.01 ). Conclusion LTA of Bifidobacterium can down-regulate the expression of survivin in LoVo cells through inhibiting the activity of PI3K/AKT signal transduction pathway and up-regulate the expression of p53. Accordingly, the activity of caspases is increased, and apoptosis of LoVo cells occurs ultimately.
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