Ott_a_217017 8751..8763

Lihua Luo Ruizhi Ran Jie Yao 3 Fang Zhang Maohui Xing Min Jin Lanqing Wang Tao Zhang 1Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, People’s Republic of China; 2Department of Oncology II, The Central Hospital of Enshi Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, Hubei 445000, People’s Republic of China; 3Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, People’s Republic of China 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 andHoechst 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 Seenriched 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.