异硫氰酸苯乙酯通过上调PTEN表达诱导肺癌细胞凋亡  

Phenethyl isothiocyanate induces human lung cancer cells apoptosis through up-regulating PTEN expression

作　　者：胡军[1] 胡名松[1] 曾慰[1] 刘翔[1] 郑达扬[1] 高文奎[1] 

机构地区：[1]南华大学附属第二医院心胸外科,湖南衡阳421001

出　　处：《中国生化药物杂志》2014年第3期36-39,43,共4页Chinese Journal of Biochemical Pharmaceutics

基　　金：湖南省自然科学基金(13JJ4079)

摘　　要：目的研究异硫氰酸苯乙酯(phenethyl isothiocyanate,PEITC)抑制肺癌细胞NCI-H446生长的机制。方法体外培养肺癌NCI-H446细胞,并分为对照组和PEITC处理组。对照组细胞给予0.1%二甲基亚砜处理,PEITC组分别用10μmol/L、30μmol/L和50μmol/L PEITC作用24 h,噻唑蓝法和流式细胞术分别检测细胞的增殖与凋亡;Western blot检测Akt磷酸化、细胞内活性caspase-3和caspase-9的表达以及胞浆中细胞色素C的含量;Real time PCR检测磷酸酯酶与张力蛋白同源物(phosphatase and tensin homologue,PTEN)mRNA水平。结果PEITC可显著抑制肺癌NCI-H446细胞增殖(P<0.05),并诱导其凋亡。PEITC处理后,肺癌细胞内活性caspase-3和caspase-9含量显著高于对照组(P<0.05);同时,PEITC处理后,肺癌细胞质中细胞色素C含量明显增高(P<0.05)。PEITC也能抑制NCI-H446细胞中Akt的磷酸化水平。此外,PEITC处理后,可明显诱导肺癌细胞内PTEN表达的增加(P<0.05),其中50μmol/L PEITC处理后,PTEN mRNA含量增高了4.6倍。结论PEITC能抑制NCI-H446肺癌细胞生长,其机制可能通过上调PETN表达,从而抑制PI3K/Akt的活性有关。Objective To investigate the anti-proliferation mechanisms of Phenethyl isothiocyanate (PEITC)in human lung cancer cells line NCI-H446. Methods Human lung cancer cell line NCI-H446 was cultured in vitro,and treated with 10,30,50μmol/L PEITC for 24 h respectively. Cell viability and apoptosis were analyzed by methylthiazolyldiphenyl-tetrazolium bromide (MTT)assay and flow cytometry,respectively. Phosphorylation of Akt,activation of caspase-3 and caspase-9 in NCI-H446 cells,and production of cytochrome C in cytoplasm were detected by Western blot. Expression of phosphatase and tensin homologue (PTEN)was detected by real-time PCR. Results PEITC significantly reduced NCI-H446 cells proliferation in dose-dependent manner (P<0.05 ),and apoptosis was also inducted after PEITC administration. PEITC also markedly induced expression of caspase-3 and caspase-9,as compared with control group. And the level of cytochrome C in the cytoplasm was also increased after treatment with PEITC.Furthermore,PEITC treatment significantly increased the mRNA level of PTEN in NCI-H446 cells. Conclusion PEITC may be used as a potential anti-lung cancer agent by regulationg PI3K/AKT pathway and increasing PETN expression.

关 键 词：异硫氰酸苯乙酯 肺肿瘤 细胞系 磷酸酯酶与张力蛋白同源物 凋亡 

分 类 号：R734.2[医药卫生—肿瘤]