氯喹对人肺癌A549细胞周期阻滞及增殖抑制的机制

发布时间：2019-04-01 12:39

【摘要】：目的探讨氯喹抑制人非小细胞肺癌A549细胞增殖、促进凋亡、阻滞细胞周期的作用及其分子机制。方法应用MTT法和流式细胞术分别检测氯喹对A549细胞增殖、细胞凋亡和细胞周期的影响;Western blotting检测氯喹对A549细胞周期蛋白(cyclinE1)和细胞周期蛋白依赖性激酶(CDK2)、肿瘤抑制蛋白PTEN以及细胞周期抑制蛋白P21、P27表达水平的影响。结果氯喹能够抑制A549细胞增殖,并且具有时间-剂量依赖性。氯喹可以诱导细胞凋亡,不同浓度的氯喹作用于A549细胞24 h后,细胞凋亡率随着作用剂量的增加而升高。进一步的研究发现,氯喹还能够阻滞细胞周期于G0/G1期,降低cyclinE1和CDK2表达水平,明显提高PTEN、P21和P27的表达水平。结论氯喹具有抑制肺癌细胞增殖、促进其凋亡和阻滞细胞周期的作用,其机制可能与其抑制Cyclin E1和CDK2表达,并且上调PTEN、P21和P27蛋白的表达有关。
[Abstract]:Aim to investigate the effects of chloroquine on proliferation, apoptosis and cell cycle arrest of human non-small cell lung cancer cell line A549 and its molecular mechanism. Methods the effects of chloroquine on proliferation, apoptosis and cell cycle of A549 cells were detected by MTT assay and flow cytometry, respectively. The effects of chloroquine on the expression of cyclin-dependent kinase (CDK2), tumor suppressor protein (PTEN), cyclin-dependent kinase (cyclinE1), cyclin-dependent kinase (CDK2), tumor suppressor protein (PTEN), cell cycle suppressor protein P21and P27 in A549 cells were detected by Western blotting. Results chloroquine could inhibit the proliferation of A549 cells in a time-dose dependent manner. Chloroquine could induce apoptosis of A549 cells. After treated with chloroquine at different concentrations for 24 h, the apoptosis rate of A549 cells increased with the increase of the dose of chloroquine. Further studies showed that chloroquine could also block the cell cycle in G0/G1 phase, decrease the expression of cyclinE1 and CDK2, and significantly increase the expression of PTEN,P21 and P27. Conclusion chloroquine can inhibit the proliferation of lung cancer cells, promote their apoptosis and block cell cycle. The mechanism of chloroquine may be related to its inhibition of Cyclin E1 and CDK2 expression, and the up-regulation of PTEN,P21 and P27 protein expression.
【作者单位】：齐齐哈尔医学院医药科学研究院;齐齐哈尔医学院基础医学院;佳木斯大学基础医学院;
【基金】：黑龙江省普通高等学校青年学术骨干支持计划(1253G066) 齐齐哈尔市科技局指令性项目(SFGG-201556)
【分类号】：R734.2

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