姜黄素下调PI3K/AKT/mTOR通路抑制人肝癌细胞系增殖

Curcumin inhibits proliferation of human hepatoma cell line via down-regulation of PI3K/AKT/mTOR signaling pathway

目的观察姜黄素对体外培养人肝癌细胞系HL-7702增殖的影响,并探讨其作用机制。方法体外培养HL-7702细胞,不同浓度的姜黄素(0、10、20、40和80μmol/L)处理48 h。PI3K/AKT抑制剂LY294002联合姜黄素处理细胞。分别用MTT法检测细胞增殖,用Western blot法检测细胞内PI3K、AKT、m TOR、Bax、Bcl-2及活化的caspase-3的蛋白含量。结果姜黄素可以浓度依赖性的抑制HL-7702细胞增殖,增加细胞中PI3K、AKT和m TOR的磷酸化水平(P<0.05)。姜黄素可诱导HL-7702细胞凋亡,增加Bax和活化的caspase-3的含量(P<0.05),减少Bcl-2的含量(P<0.05)。LY294002与姜黄素联用后,姜黄素对细胞增殖及凋亡无明显作用。结论姜黄素可抑制人肝癌细胞系HL-7702增殖,诱导细胞凋亡,作用机制可能与其下调PIK/AKT/m TOR信号通路的活性有关。

Objective The effect of curcumin on human hepatoma cell line HL-7702 proliferation and the inhibitory mechanism was investigated. Methods HL-7702 cultured in vitro was treated with gradient concentrations of curcu- min（0, 10, 20,40, 80 μmol/L）for 48 hours or subjected to combinational treatment of PI3K/AKT inhibitor LY294002 with curcumin. Then MTT was applied to detect cell proliferation and Western blot was used to detect PI3 K, AKT, mTOR, Bax, Bcl-2 protein level and caspase-3 activation. Results Cureumin inhibited HL-7702 prolif- eration in a dose-dependent manner via upregulating phosphorylation of PI3K, AKT and mTOR. Curcumin induced apoptosis of HL-7702 cells with increased Bax and caspase-3 activation as well as decreased Bcl-2. In addition, LY294002 attenuated the effect of curcumin over cell proliferation and apoptosis. Conclusions Curcumin inhibites proliferation and triggers apoptosis of human hepatoma cell line HL-7702, which may be caused by the downregu- lating PI3K/AKT/mTOR signaling pathway.