Se-Enriched Cordyceps militaris Inhibits Cell Proliferation, Induces Cell Apoptosis, And Causes G2/M Phase Arrest In Human Non-Small Cell Lung Cancer Cells
Se-Enriched Cordyceps militaris Inhibits Cell Proliferation, Induces Cell Apoptosis, And Causes G2/M Phase Arrest In Human Non-Small Cell Lung Cancer Cells
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富硒蛹虫草抑制人非小细胞肺癌细胞增殖、诱导细胞凋亡并导致 G2/M 期阻滞
DOI：
10.2147/ott.s217017
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发表时间：
2019-01-01
影响因子：
4
通讯作者：
Zhang, Tao
中科院分区：
文献类型：
--
作者：
Luo, Lihua;Ran, Ruizhi;Zhang, Tao
背景：已有文献报道了皮质醇对多种肿瘤的抗肿瘤作用。然而，关于富硒蛹虫草在非小细胞肺癌（NSCLC）中的作用知之甚少。本研究探讨富硒蛹虫草对非小细胞肺癌细胞株NCI-H292和A549细胞增殖、凋亡和细胞周期的影响。方法采用CCK-8法测定富硒蛹虫草对非小细胞肺癌细胞NCI-H292和A549的作用浓度。分别采用集落形成实验、流式细胞术和Hoechst 33342染色实验以及流式细胞术分析来评估富硒蛹虫草对NSCLC细胞活力、细胞凋亡和细胞周期分布的影响。最后，分别采用qPCR和Western blot检测富硒蛹虫草对促凋亡基因BAX和抗凋亡基因BCL-2以及G2/M期细胞周期调控蛋白CDK 1和cyclin B1表达的影响。结果富硒蛹虫草对NCI-H292细胞的作用浓度为0、4、8、12 mg/mL，对A549细胞的作用浓度为0、12.5、25、50 mg/mL。用增加的富硒蛹虫草处理的NSCLC细胞显示出抑制的细胞活力。富硒蛹虫草可诱导NSCLC细胞凋亡，且呈浓度依赖性。结论：富硒蛹虫草在mRNA和蛋白水平上降低了NSCLC细胞中抗凋亡成员BCL-2和促凋亡成员BAX的比例。加硒蛹虫草处理的NSCLC细胞G2/M期细胞比例增加。G2/M期细胞周期调控蛋白CDK 1和cyclin B1在mRNA和蛋白水平的下调进一步证实了富硒蛹虫草对细胞周期的影响。结论富硒蛹虫草对NSCLC细胞增殖具有抑制作用，对细胞凋亡和细胞周期有促进作用，为NSCLC的治疗提供了新的思路。
Background The anticancer effects of cordyceps on various tumors have been reported. However, little is known about the role of selenium (Se)-enriched Cordyceps militaris in non-small cell lung cancer (NSCLC). In this study, the effects of Se-enriched Cordyceps militaris on cell proliferation, cell apoptosis and cell cycle in NSCLC cell line NCI-H292 and A549 were investigated. Methods CCK-8 assay was used to determine the appropriate concentrations of Se-enriched Cordyceps militaris in NSCLC (namely NCI-H292 and A549) cells. Colony formation assay, flow cytometric and Hoechst 33342 staining assays, and flow cytometric analysis were separately employed to assess the effect of increased Se-enriched Cordyceps militaris on NSCLC cell viability, cell apoptosis and cell-cycle distribution. Finally, the qPCR and Western blot assays were, respectively, applied to evaluate the effects of Se-enriched Cordyceps militaris on the expression of pro-apoptotic member BAX and the anti-apoptotic member BCL-2, as well as of G2/M cell cycle regulatory proteins CDK1 and cyclin B1. Results The concentration of Se-enriched Cordyceps militaris was 0, 4, 8, 12 mg/mL for NCI-H292 cells, and 0, 12.5, 25, 50 mg/mL for A549 cells. NSCLC cells treated with increased Se-enriched Cordyceps militaris showed the inhibited cell viability. Se-enriched Cordyceps militaris induced NSCLC cell apoptosis in concentration-dependent manner. Consistently, Se-enriched Cordyceps militaris diminished the ratio of anti-apoptotic member BCL-2 and pro-apoptotic member BAX at mRNA and protein levels in NSCLC cells. The percentage in G2/M phase was increased in NSCLC cells treated with increased Se-enriched Cordyceps militaris. Downregulation of G2/M cell cycle regulatory proteins CDK1 and cyclin B1 at mRNA and protein levels in NSCLC cells further confirmed the effects of Se-enriched Cordyceps militaris on cell cycle. Conclusion This study demonstrated the inhibitory role of Se-enriched Cordyceps militaris in cell proliferation and its facilitating role in cell apoptosis and cell cycle in NSCLC cells, suggesting an alternative therapeutic strategy for NSCLC treatment.