>
网站首页期刊介绍通知公告编 委 会投稿须知电子期刊广告合作联系我们
最新消息:
Mcl-1抑制剂UMI-77诱导胆囊癌细胞GBC-SD凋亡的机制研究
作者:张生彬  刘宝琴  董长城  李冰 
单位:内蒙古包钢医院 肝胆外科, 内蒙古 包头 014010
关键词:Mcl-1抑制剂 UMI-77 胆囊癌 细胞凋亡 
分类号:R735.8
出版年·卷·期(页码):2018·37·第五期(771-776)
摘要:

目的:探讨髓样细胞白血病-1(Mcl-1)抑制剂UMI-77诱导胆囊癌细胞GBC-SD凋亡的机制。方法:采用不同浓度的UMI-77处理胆囊癌GBC-SD细胞,MTT比色法和Annexin V/PI分别检测细胞增殖和细胞凋亡情况;Western blotting检测UMI-77作用后细胞中Mcl-1、Bcl-2、Bcl-xL、Bax、Bak、cleaved-caspase 9、cleaved-caspase 3和cleaved-PARP蛋白的表达。结果:MTT检测结果显示,不同浓度的UMI-77分别作用于GBC-SD细胞后均对细胞增殖产生不同程度的抑制作用,且呈剂量依赖性和时间依赖性。Annexin V/PI检测结果显示,随着UMI-77作用浓度的升高,细胞凋亡率逐渐增加,且呈剂量依赖性。Western blotting结果显示,10 μmol·L-1 UMI-77处理GBC-SD细胞24 h后,其抗凋亡蛋白Mcl-1的表达量显著降低(P<0.05),促凋亡蛋白Bax和Bak的表达量显著升高(P<0.05),但Bcl-2和Bcl-xL的蛋白表达量无显著性变化,且其cleaved-caspase 9、cleaved-caspase 3和cleaved-PARP蛋白的表达量均显著升高(P<0.05)。结论:Mcl-1抑制剂UMI-77可通过caspase介导的内源性凋亡途径诱导胆囊癌GBC-SD细胞发生凋亡,且呈剂量依赖性,因此,Mcl-1可能成为胆囊癌研究中一个新的治疗靶点。

Objective:To investigate the mechanism of apoptosis induced by myeloid cell leukemia-1 (Mcl-1) inhibitor UMI-77 on gallbladder carcinoma GBC-SD cells. Methods:GBC-SD cells were treated with different concentrations of UMI-77. The proliferation and apoptosis of GBC-SD cells were detected by MTT assay and Annexin V/PI. The expressions of Mcl-1, Bcl-2 Bcl-xL, Bax, Bak, leaved-caspase 9, cleaved-caspase 3 and cleaved-PARP protein in GBC-SD cells after treated with UMI-77 were detected by western blotting. Results:The results of MTT showed that different concentrations of UMI-77 had different inhibitory effects on cell proliferation of GBC-SD cells in a dose-dependent and time-dependent manner. Annexin V/PI test results showed that the apoptotic rate increased gradually with the increase of UMI-77 concentration in a dose-dependent manner. Western blotting showed that the expression of anti-apoptotic protein Mcl-1 was significantly decreased (P<0.05), and the expressions of Bax and Bak proteins were significantly increased (P<0.05), but the expressions of Bcl-2 and Bcl-xL proteins had no statistical significance, and the expression levels of cleaved-caspase 9, cleaved-caspase 3 and cleaved-PARP proteins were significantly increased (P<0.05) after treatment with 10 μmol·L-1 UMI-77 for 24 h. Conclusion:Mcl-1 inhibitor UMI-77 can induce apoptosis of GBC-SD cells in a dose-dependent manner by caspase-mediated endogenous apoptosis pathway, therefore, Mcl-1 may become a new therapeutic target in the gallbladder cancer research.

参考文献:

[1] HUNDAL R,SHAFFER E A.Gallbladder cancer:epidemiology and outcome[J].Clin Epidemiol,2014,6(1):99-109.
[2] 张斌,陶健,赵慈宝,等.HMGB1对胆囊癌细胞增殖、凋亡的影响及其机制研究[J].现代医学,2017,45(10):1422-1426.
[3] HANAHAN D,WEINBERG R A.Hallmarks of cancer:the next generation[J].Cell,2011,144(5):646-674.
[4] KELLY G,STRASSER A.The essential role of evasion from cell death in cancer[J].Adv Cancer Res,2011,111:39-96.
[5] ANILKUMAR U,PREHN J H M.Anti-apoptotic BCL-2 family proteins in acute neural injury[J].Front Cell Neurosci,2014,8:281.
[6] 倪俊,曹利平.胆囊癌细胞增殖与凋亡分子机制的研究进展[J].中国医刊,2003,38(10):34-36.
[7] 房佳惠,杨巍.Bcl-2家族蛋白对心肌细胞凋亡作用的研究进展[J].现代医学,2017,45(7):996-1000.
[8] KIPRIANOVA I,REMY J,MILOSCH N,et al.Sorafenib Sensitizes Glioma Cells to the BH3 Mimetic ABT-737 by Targeting MCL1 in a STAT3-Dependent Manner[J].Neoplasia,2015,17(7):564-573.
[9] ABULWERDI F,LIAO C,LIU M,et al.A novel small-molecule inhibitor of mcl-1 blocks pancreatic cancer growth in vitro and in vivo[J].Mol Cancer Ther,2014,13(3):565-575.
[10] JAIN K,SREENIVAS V,VELPANDIAN T,et al.Risk factors for gallbladder cancer:a case-control study[J].Int J Cancer,2013,132(7):1660-1666.
[11] PERCIAVALLE R M,OPFERMAN J T.Delving deeper:MCL-1's contributions to normal and cancer biology[J].Trends Cell Biol,2013,23(1):22-29.
[12] 杨侠,王瑞,徐凯,等.敲低髓细胞白血病基因1(MCL-1)促进前列腺癌细胞的增殖并促进其凋亡[J].细胞与分子免疫学杂志,2017,33(1):62-66.
[13] MOLDOVEANU T,FOLLIS A V,KRIWACKI R W,et al.Many players in BCL-2 family affairs[J].Trends Biochem Sci,2014,39(3):101-110.
[14] 姚佳慧,王义仁,周楠,等.Mcl-1小分子抑制剂在肿瘤治疗中的应用进展[J].西北药学杂志,2016,31(5):547-552.
[15] 徐神春,韩峻松,李跃.肿瘤治疗中小分子激酶抑制剂的研究进展[J].生命科学,2016(7):786-792.
[16] 朱雪萍,吴萍,张林杰.Mcl-1抑制剂UMI-77诱导胃癌细胞MGC-803凋亡的机制研究[J].安徽医科大学学报,2016,51(4):506-511.
[17] 李小艳,包素珍.Caspase家族的研究进展[J].内蒙古中医药,2012,31(2):107.

服务与反馈:
文章下载】【发表评论】【查看评论】【加入收藏
提示:您还未登录,请登录!点此登录
您是第 155013 位访问者


copyright ©《东南大学学报(医学版)》编辑部
联系电话:025-87232483 83272481
电子邮件:
bjb@pub.seu.edu.cn

苏ICP备09058364