他汀药物对p53突变肿瘤细胞的作用及机制

发布时间：2018-02-21 03:28

本文关键词： 他汀突变p 凋亡　出处：《中国老年学杂志》2017年04期 　论文类型：期刊论文

【摘要】：目的研究他汀药物对p53突变的肿瘤细胞的作用及分子机制。方法采用具有突变p53背景的人结肠癌HT29细胞,通过MTT实验检测他汀药物对细胞增殖的影响,用Western印迹检测他汀药物浓度梯度和时间梯度处理后细胞内突变p53,分子伴侣热休克蛋白(HSP)90、p53信号通路下游靶蛋白PUMA、p21、凋亡相关蛋白PARP的表达情况。结果 MTT实验结果显示,他汀药物会显著抑制HT29细胞的增殖,美伐他汀IC50为(39.95±3.81)μmol/L,辛伐他汀IC50为(24.99±0.70)μmol/L。Western印迹结果显示,随着浓度和时间梯度增加,突变p53和HSP90表达水平没有改变,但是,p53下游靶蛋白PUMA、p21的表达水平升高,PARP蛋白切割增强。结论他汀药物能够抑制p53突变的肿瘤细胞的增殖,其机制可能是将突变型p53恢复为野生型p53从而发挥其转录激活下游靶基因的功能。
[Abstract]:Objective to study the effect and molecular mechanism of statins on p53 mutant tumor cells. Methods the effects of statins on the proliferation of human colon cancer HT29 cells with mutant p53 background were detected by MTT assay. Western blot was used to detect the expression of apoptosis-related protein (PARP), the downstream target protein PUMA-p21 of the molecular chaperone heat shock protein (HSP90) and p53, after treatment with statin concentration gradient and time gradient. Statin significantly inhibited the proliferation of HT29 cells. The results of mol/L.Western blotting showed that the expression of mutant p53 and HSP90 did not change with the increase of concentration and time gradient. The results showed that mevastatin IC50 was 39.95 卤3.81 渭 mol / L, simvastatin IC50 was 24.99 卤0.70 渭 mol/L.Western blotting. However, the expression level of p53 downstream protein PUMA-p21 was increased and PARP protein cleavage was enhanced. Conclusion statins can inhibit the proliferation of p53 mutant tumor cells. The mechanism may be to restore mutant p53 to wild-type p53 and play its role in transcription activation of downstream target genes.
【作者单位】：昆明理工大学医学院衰老与肿瘤分子遗传学实验室;
【基金】：国家自然科学基金(81560601) 云南省自然科学基金项目(2014FD011)
【分类号】：R96

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