右旋硫辛酸对人肝癌HepG2细胞生长增殖及其相关机制研究

发布时间：2018-03-06 17:18

本文选题：右旋硫辛酸　切入点：HepG　出处：《中国药科大学学报》2017年03期 　论文类型：期刊论文

【摘要】：研究天然抗氧化剂右旋硫辛酸对人肝癌HepG2细胞生长、增殖的影响及其相关机制。采用MTT检测细胞增殖情况,活性氧试剂盒分析细胞内ROS水平。流式细胞术和Hoechst 33258染色观察细胞凋亡和形态变化。Western blot检测凋亡、自噬以及相关通路蛋白表达,包括Bax、Bcl-2、caspase 3、PARP、ATG5、ATG7、LC3、Beclin1、mTOR、P70S6K、P38、P53、ERK、Akt、MEK等。结果表明,经不同浓度不同时间药物处理,右旋硫辛酸可抑制HepG2细胞增殖,提高细胞内ROS水平,并呈时间和剂量依赖性。右旋硫辛酸通过上调促凋亡蛋白Bax,激活caspase家族,从而激活凋亡效应蛋白caspase 3和PARP,同时右旋硫辛酸还可上调自噬相关蛋白ATG5、ATG7、Beclin1、LC3水平,抑制磷酸化mTOR和P70S6K,激活自噬。通路研究表明:右旋硫辛酸可上调磷酸化的P38和JNK促凋亡通路促进凋亡,抑制磷酸化Akt、ERK的表达。添加自噬抑制剂3-甲基腺嘌呤后,明显抑制自噬发生。因此,右旋硫辛酸可能通过调控P38/AMPK-JNK,PI3K/Akt和Ras/Raf/MEK/ERK途径激活自噬,诱导细胞凋亡。
[Abstract]:Study on natural antioxidants lipoic acid on the growth of human right liver cancer cell HepG2 proliferation and its mechanism. The cell proliferation was detected by MTT, ROS kit analysis of intracellular levels of ROS. Flow cytometry and Hoechst 33258 staining was used to observe the apoptosis and morphological changes of.Western blot expression, apoptosis, autophagy and related pathways including protein Bax, Bcl-2, caspase 3, PARP, ATG5, ATG7, LC3, Beclin1, mTOR, P70S6K, P38, P53, ERK, Akt, MEK. The results showed that the drug treatment of different concentration at different time, dextran lipoic acid can inhibit the proliferation of HepG2 cells, increase the level of ROS cells in dose and time dependent dextrorotation. Lipoic acid by up regulation of Pro apoptotic protein Bax, caspase activation, leading to activation of apoptosis protein caspase 3 and PARP, at the same time - lipoic acid can upregulate autophagy related protein ATG5, ATG7, Beclin1, LC3, and Preparation of mTOR and P70S6K phosphorylation, activation of autophagy. Research shows that dextran lipoic acid pathway can increase the phosphorylation of P38 and JNK apoptosis pathway to promote apoptosis, inhibit the phosphorylation of Akt and ERK. The expression of autophagy inhibitor 3- after adding methyl adenine, inhibit autophagy. Therefore, dextran lipoic acid can regulate P38/AMPK-JNK, PI3K/Akt Ras/Raf/MEK/ERK pathway and activation of autophagy, apoptosis.

【作者单位】：南京工业大学;
【分类号】：R96

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