苦参碱通过抑制PI3K/AKT/mTOR通路促进非小细胞肺癌A549 细胞的自噬和凋亡 |
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引用本文: | 郝艳梅,殷红梅,朱超莽,李凤,张英杰,李玉云,王效静,李多杰.苦参碱通过抑制PI3K/AKT/mTOR通路促进非小细胞肺癌A549 细胞的自噬和凋亡[J].南方医科大学学报,2019,39(7):760. |
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作者姓名: | 郝艳梅 殷红梅 朱超莽 李凤 张英杰 李玉云 王效静 李多杰 |
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摘 要: | 目的探讨苦参碱对非小细胞肺A549细胞增殖的抑制作用及潜在的分子机制。方法苦参碱(终浓度为0、0.4、0.8、1.2、
1.6、2.0 g/L)处理非小细胞肺癌A549细胞24、48、72 h,采用CCK-8检测A549细胞的存活情况,荧光显微镜下观察A549细胞的
形态学变化,流式细胞术(FCM)分析细胞凋亡情况,Western blot 分析苦参碱和PI3K特异性抑制剂LY294002(10 nmol/L)对
A549细胞AKT信号通路和自噬相关蛋白的影响。结果苦参碱对A549细胞增殖的抑制作用呈时间-剂量依赖性(P<0.05),当
苦参碱浓度达到1.6 g/L时,细胞萎缩加剧,细胞碎片和悬浮细胞明显增多,吖啶橙染色,可以观察到自噬液泡。FCM分析显示
随着苦参碱浓度增加,细胞凋亡率也升高,浓度为0.8~1.6 g/L的苦参碱诱导细胞凋亡呈时间和剂量依赖性增加。同时,1.6 g/L苦
参碱和LY294002(10 nmol/L)组p-AKT、p-mTOR蛋白表达水平较对照组明显减低(P<0.05),自噬相关轻链蛋白3B(LC 3B)表
达水平高于对照组(P<0.05)。结论苦参碱通过抑制PI3K/AKT/mTOR信号通路的活性,抑制A549细胞增殖,诱导细胞自噬和
凋亡,苦参碱可能是一种潜在的肺癌治疗药物。
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Matrine inhibits proliferation and promotes autophagy and apoptosis in non-small cell
lung cancer cells by deactivating PI3K/AKT/mTOR pathway |
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Abstract: | Objective To investigate the inhibitory effect of matrine on the proliferation of human non-small cell lung cancer
(NSCLC) and explore the possible molecular mechanism. Methods Cultured human NSCLC A549 cells were treated with 0.4,
0.8, 1.2, 1.6, and 2.0 g/L matrine for 24, 48 or 72 h. CCK-8 assay was used for measuring the changes in A549 cell viability. The
morphological changes of the cells were observed under a fluorescence microscope, and flow cytometry was employed for
analyzing the cell apoptosis. The effects of matrine and the PI3K specific inhibitor LY294002 (10 nmol/L) on AKT pathway and
autophagy-related proteins in A549 cells were investigated using Western blotting. Results Matrine significantly inhibited the
proliferation of A549 cells in a time- and dose-dependent manner (P<0.05). At the concentration of 1.6 g/L or higher, matrine
caused obvious cell shrinkage and fragmentation and significantly increased floating cells; autophagy vacuoles could be
observed in the cells after acridine orange staining. Within the concentrations range of 0.8-1.6 g/L, matrine time- and dosedependently
increased the cell apoptosis. Treatment of the cells with 1.6 g/L matrine and 10 nmol/L LY294002 resulted in
significantly lowered expressions of p-AKT and p-mTOR proteins and increased the expression of light chain 3B (LC 3B), an
autophagy-related protein, as compared with those in the control cells (P<0.05). Conclusion We demonstrate that matrine
inhibits the proliferation and induces autophagy and apoptosis of A549 cells by deactivating AKT pathway, suggesting the
potential of matrine as an anti-cancer agent for lung cancer. |
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