[1]郝艳梅,殷红梅,朱超莽,等.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,(07):760.[doi:10.12122/j.issn.1673-4254.2019.07.02]
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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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《南方医科大学学报》[ISSN:1673-4254/CN:44-1627/R]

卷:
期数:
2019年07期
页码:
760
栏目:
出版日期:
2019-07-15

文章信息/Info

Title:
Matrine inhibits proliferation and promotes autophagy and apoptosis in non-small cell lung cancer cells by deactivating PI3K/AKT/mTOR pathway
作者:
郝艳梅殷红梅朱超莽李凤张英杰李玉云王效静李多杰
关键词:
苦参碱凋亡自噬AKT信号通路非小细胞肺癌
Keywords:
matrine apoptosis autophagy AKT pathway non-small cell lung cancer
DOI:
10.12122/j.issn.1673-4254.2019.07.02
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。
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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更新日期/Last Update: 1900-01-01