麦角甾醇衍生物通过抑制NF-κB通路诱导人宫颈癌HeLa细胞凋亡  

Ergosterol Derivatives Induce Apoptosis of Human Cervical Cancer HeLa Cells via NF-κB Pathway

作　　者：肖琳[1] 刘明[2] 刘格 吴宁 林秀坤[4] XiAO Lin;LiU Ming;LiU Ge;WU Ning;LiN Xiukun(College of Chemistry and Pharmaceutical Sciences,Qingdao Agricultural University,Qingdao,Shandong,266109,China;Schoal of Medicine and Pharmacy,Ocean University of China,Qingdao,Shandong,266003,China;Institute of Oceanalogy,Chinese Academy of Science,Qingdao,Shandong,266071,China;Depament of Pharmacalogy,Capital Medical UTffversity,Beijing,100069,China)

机构地区：[1]青岛农业大学化学与药学院,山东青岛266109 [2]中国海洋大学医药学院,山东青岛266003 [3]中国科学院大学海洋所,山东青岛266071 [4]首都医科大学药理系,北京100069

出　　处：《肿瘤药学》2018年第4期512-518,共7页Anti-Tumor Pharmacy

基　　金：山东省重点研发计划(2018GSF121036)

摘　　要：目的探讨麦角甾醇衍生物(ED)对人宫颈癌HeLa细胞凋亡的影响及其可能机制。方法采用MTT法测定ED对人宫颈癌HeLa细胞增殖的影响,流式细胞检测ED对HeLa细胞周期的影响,Hoechst 33258染色测定ED对HeLa细胞凋亡的影响,免疫荧光分析ED对HeLa细胞NF-κB p65复合物的细胞内定位的影响,Western blot检测ED对HeLa细胞NF-κB信号通路相关蛋白表达的影响。结果 ED对HeLa细胞的IC50值为(9.1±1.64)μg·m L^(-1),可使HeLa细胞周期阻滞于S期,诱导HeLa细胞凋亡,抑制HeLa细胞中NF-κB的活化和核转位,减少NF-κB依赖的Bcl-2、Survivin、COX-2和VEGF蛋白的表达。结论ED可能通过抑制NF-κB信号通路活化,减少Bcl-2、Survivin、COX-2和VEGF蛋白的表达,诱导宫颈癌HeLa细胞凋亡。Objective To investigate the possible mechanism in the process of ergosterol derivatives （ED）-induced hmnan HeLa cancer cellsapoptosis and related molecular mechanisms. Methods MTT assay was used to detect the cytotoxicity of ED against human cancer cells. Apoptosis was determined by Hoechst 33258 staining assay. Cell cycle arrestwas measured by flow cytometry. Western blot assay was used to detect the expression of NF-kB-dependent genes. NF-kB p65 nuclear translocation was determined by inmmnofluorescence analysis. Results ED displayed potent cytotoxic activity to a wide range of human tremor cell lines; the IC50 of ED on HeLa cells was （9.1 ± 1.64） gg.mLI. Treat- merit of HeLa cells with ED resulted in cell cycle arrest in S phase. Further study revealed that ED could induce remarkable apoptosis. Treat- merit of the cancer cells with ED resulted in inhibition of NF- K B p65 activation and nuclear translocation. The expression of NF-kB-dependent genes, including Bcl-2, Survivin, COX-2 and VEGF, were also significantly attenuated. Conclusion These studies suggested that ED induced cell death and apoptosis via NF-kB signaling pathway and inhibiting expression of Bcl-2, Survivin, COX-2 and VEGF in HeLa cells.

关 键 词：麦角甾醇衍生物 NF-ΚB HELA细胞 细胞凋亡 

分 类 号：R969.1[医药卫生—药理学] R285.6[医药卫生—药学]