抑癌因子p53介导的阿托伐他汀致HePG2细胞焦亡的作用研究  

Effects of tumor suppressor p53-mediated Atorvastatin in inducing pyroptosis of HepG2 cells

作　　者：黄璐 巫传玲[1] 邓晶晶[1] Huang Lu;Wu Chuanling;Deng Jingjing(School of Pharmacy,Chengdu Medical College,Chengdu,Sichuan,610500,China)

机构地区：[1]成都医学院药学院,成都610500

出　　处：《西南国防医药》2020年第8期705-709,共5页Medical Journal of National Defending Forces in Southwest China

基　　金：2017年度四川省省级大学生创新训练项目(201713705100)。

摘　　要：目的通过p53小干扰RNA(p53siRNA)构建p53表达差异的肝癌细胞模型,探讨p53表达量对阿托伐他汀(Atorvastatin)诱导肝癌细胞HepG2焦亡的影响。方法p53siRNA构建HepG2细胞的p53的表达差异,通过MTT,qPCR和Western blot检测,明确p53表达量高低是否对Atorvastatin对HepG2细胞生长抑制作用和焦亡诱导的存在影响。结果HepG2细胞生长率在p53siRNA干预后未见明显影响(P>0.05);Atorvastatin处理后能显著增加人肝癌HepG2细胞p53在mRNA(P<0.05)和蛋白水平的表达,而对p53敲低的HepG2细胞生长抑制率明显降低(P<0.05);p53siRNA能明显降低Atorvastatin诱导LDH的释放水平(P<0.05),阻止了Atorvastatin升高的IL-1β、IL-18和caspase-1的蛋白表达。结论Atorvastatin可能通过促进焦亡,抑制了肝癌细胞的增殖,即显示了细胞焦亡可能是Atorvastatin抑制肝癌细胞的有效途径,其过程受到p53表达量的调节。这一研究完善了Atorvastatin对肝癌作用机制体系,可能为肝癌的防治办法的探索提供新的思路。Objective To explore the effect of p53 expression on Atorvastatin inducing pyroptosis of liver carcinoma(HepG2) cells by constructing a liver carcinoma model with p53 expression differences via p53 small interfering RNA(p53 siRNA). Methods The expression difference of p53 in HepG2 cells was constructed by p53 siRNA. Methyl-thiazolyl-tetrazolium(MTT) assay, quantitative polymerase chain reaction(qPCR) and western blot analysis were utilized to determine whether the expression level of p53 influenced Atorvastatin inhibiting the growth of HepG2 cells and inducing the pyroptosis. Results The growth rate of HepG2 cells was not significantly affected after the intervention of p53 siRNA(P > 0.05). Atorvastatin that has been regulated significantly increased the expression level of p53 of human liver carcinoma(HepG2) cells in mRNA(P < 0.05) and protein, and notably lowered the inhibition on the growth of HepG2 cells knocked down by p53(P < 0.05). p53 siRNA significantly reduced the level of Atorvastatin inducing LDH release(P < 0.05), and curbed the protein expression of IL-1β, IL-18, and caspase-1 increased by Atorvastatin. Conclusion Atorvastatin may inhibit the proliferation of liver carcinoma cells by promoting pyroptosis, which indicates that pyroptosis may be an effective approach for Atorvastatin to suppress liver cancer cells, of which the process is regulated by p53 expression. This study has perfected the mechanism of Atorvastatin on liver cancer and may provide new insights for the exploration of the prevention and treatment of liver cancer.

关 键 词：抑癌因子p53 阿托伐他汀 HEPG2细胞 焦亡 

分 类 号：R735.7[医药卫生—肿瘤]