氯喹对人肺癌A549细胞周期阻滞及增殖抑制的机制

朱文斌 于海涛 刘立琨 李鹏辉 张微 岳丽玲*

doi:10.16098/j.issn.0529-1356.2017.06.010

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解剖学报 ›› 2017, Vol. 48 ›› Issue (6) : 693-697. DOI: 10.16098/j.issn.0529-1356.2017.06.010

肿瘤生物学

氯喹对人肺癌A549细胞周期阻滞及增殖抑制的机制

朱文斌¹于海涛²刘立琨¹李鹏辉² 张微^1,3 岳丽玲^1*

作者信息 +

Mechanism of the induction of cell cycle arrest and inhibition on A549 cells by chloroquine

ZHU Wen-bin¹ YU Hai-tao^２ LIU Li-kun^１LI Peng-hui^２ ZHANG Wei^1,3 YUE Li-ling^1*

Author information +

文章历史 +

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(cyclin E1)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24h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CyclinE1和CDK2表达，并且上调PTEN、P21和P27蛋白的表达有关。

Abstract

Objective To investigate the effect of chloroquine on proliferation, apoptosis and cell cycle of human non-small cell lung cancer A549 cells and to explore the mechanism. Methods MTT assay was used to examin the A549 cells that were treated with chloroquine. The alteration of apoptosis rate and cell cycle was detected by flow cytometry. The expression of cell-cycle regulating proteins cyclin E1, cyclin dependent kinase (CDK2)，tumour suppressor protein PTEN and cell cycle inhibitory proteins P21 and P27 were examined with Western blotting. Results Chloroquine significantly inhibited cell proliferation of A549 cells in a time-and dose-dependent manner. Chloroquine also induced apoptosis. The rate of cell apoptosis was increased in a dose-dependent manner in A549 cells that were treated with various dose of chloroquine for 24 hours. Furthermore, chloroquine arrested the cell cycle at G₀/G₁ phase, decreased the protein expression level of cyclinE1 and CDK2, but significantly increased the protein expression level of PTEN, P21 and P27. Conclusion Chloroquine may inhibit the lung cancer cell proliferation, accelerate its apoptosis and arrest cell cycle processes. The mechanism may be related with the inhibition of expression of cyclinE1 and CDK2 and up-regulation of expression of PTEN, P21and P27.

导出引用

朱文斌于海涛刘立琨李鹏辉张微岳丽玲. 氯喹对人肺癌A549细胞周期阻滞及增殖抑制的机制[J]. 解剖学报. 2017, 48(6): 693-697 https://doi.org/10.16098/j.issn.0529-1356.2017.06.010

ZHU Wen-bin YU Hai-tao LIU Li-kun LI Peng-hui ZHANG Wei YUE Li-ling. Mechanism of the induction of cell cycle arrest and inhibition on A549 cells by chloroquine[J]. Acta Anatomica Sinica. 2017, 48(6): 693-697 https://doi.org/10.16098/j.issn.0529-1356.2017.06.010

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