他汀药物对p53突变肿瘤细胞的作用及机制  

The effect and mechanism of statins on p53 mutant tumor cells

作　　者：牟汉川 杨志宽[1] 暴亚锋 王玉玲[1] 刘静[1] 张继虹[1] 

机构地区：[1]昆明理工大学医学院衰老与肿瘤分子遗传学实验室,云南昆明650500

出　　处：《中国老年学杂志》2017年第4期788-790,共3页Chinese Journal of Gerontology

基　　金：国家自然科学基金(81560601);云南省自然科学基金项目(2014FD011)

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。Objective To explore the effect of statins on p53 mutant tumor cells and the underlying molecular mechanism.Methods The human mutant p53 colon cancer cells HT29（ p53 mutant） were in vitro cultured. Cell proliferation was tested by MTT method. The expression of molecular chaperones HSP90,p53 target genes PUMA and p21,apoptosis-related protein PARP were measured by Western blot.Results Statins significantly inhibited the proliferation of HT29 cells,treatment with mevastatin exhibited an IC50 value of（ 39. 95 ±3. 81） μmol / L,the simvastatin exhibited an IC50 value of（ 24.99±0.70） μmol / L.Compared with those of control group,the protein expressions of mutant p53 and HSP90 were not affected,but statins significantly upregulated the protein expressions of PUMA,p21,and PARP.Conclusions Statins could inhibit the growth of HT29 cells,upregulation of p53 target genes PUMA and p21,but had no effect on the expression of mutant p53,demonstrates that it is possible to restore p53 responses in p53 mutant cells.

关 键 词：他汀 突变P53 凋亡 

分 类 号：R73[医药卫生—肿瘤]