新化合物TDB通过PI3K/Akt通路抑制人肝癌SMMC-7721细胞增殖并诱导其凋亡  

Novel compound TDB inhibits proliferation and induces apoptosis of human hepatocellular carcinoma SMMC-7721 cells via PI3K/Akt signal pathway

作　　者：林春华 肖敏 劳基通 杨照新 田树红 符健(指导) LIN Chun-Hua;XIAO Min;LAO Ji-Tong;YANG Zhao-Xin;TIAN Shu-Hong;FU Jian(Hainan Province Key Lab of Drug Preclinical Pharmacology & Toxicology Research,Hainan Medical University,Haikou 571199,China)

机构地区：[1]海南医学院,海南省药物临床前药理毒理学研究重点实验室,海口571199

出　　处：《中国免疫学杂志》2020年第7期826-831,共6页Chinese Journal of Immunology

基　　金：海南省重大项目“药物安全性评价平台”课题(No.ZDKJ2016001-02)资助项目。

摘　　要：目的:观察新化合物TDB抑制人肝癌SMMC-7721细胞增殖并诱导其凋亡的作用及其可能的作用机制。方法:采用不同浓度的TDB处理人肝癌SMMC-7721细胞48 h,以MTT法检测细胞增殖,流式细胞仪检测细胞周期和细胞凋亡,Western blot法检测Bax、Bcl-2、Cleaved Caspase-3、Akt和p-Akt等蛋白的表达情况。结果:TDB能呈浓度依赖性抑制肝癌细胞增殖,阻滞细胞周期于S期,诱导细胞凋亡;同时下调p-Akt、Bcl-2表达,上调Bax、Cleaved Caspase-3表达。结论:TDB具有抑制肝癌细胞增殖、阻滞细胞周期和诱导细胞凋亡作用,其机制可能与抑制肝癌细胞PI3K/Akt通路,改变Bcl-2/Bax间的平衡,激活下游效应型Caspases发挥诱导凋亡作用有关。Objective:To observe the inhibitory effect of the new compound TDB on the proliferation and apoptosis of human hepatocellular carcinoma SMMC-7721 cells,and to explore the possible mechanism.Methods:Human hepatocellular carcinoma SMMC-7721 cells were treated with different concentrations of TDB for 48 h.MTT assay was used to detect cell proliferation,and flow cytometry was used to detect cell cycle and apoptosis.Protein expression of Bax,Bcl-2,Cleaved Caspase-3,Akt and p-Akt were detected by Western blot.Results:TDB could inhibit the proliferation of human hepatocellular carcinoma SMMC-7721 cells in a concentration-dependent manner,arrest the cell cycle in S phase,and induce apoptosis;at the same time,the expression of p-Akt,Bcl-2 were down-regulated with the increase of TDB,while the expression of Bax,Cleaved Caspase-3 were increased.Conclusion:TDB can suppress the proliferation,arrest cell cycle and induce apoptosis of human hepatocellular carcinoma SMMC-7721.The mechanism may be related to inhibiting the PI3K/Akt pathway,changing the balance between Bcl-2/Bax,and activating downstream effector Caspases to induce apoptosis.

关 键 词：苯并噁唑 SMMC-7721 增殖 凋亡 PI3K/AKT 

分 类 号：R965.1[医药卫生—药理学] R979.1[医药卫生—药学]