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靶向阻断Hedgehog信号通路对结肠癌细胞增殖的影响及机制

发表时间:2014-06-15  浏览量:2038  下载量:658
全部作者: 王军,董卫国,郭绪峰,宋佳,余世界,刘敏
作者单位: 武汉大学人民医院消化内科,消化系统疾病湖北省重点实验室
摘 要: 目的:探讨Hedgehog(Hh)信号通路在结肠癌细胞中增殖和凋亡的作用。方法:选取人结肠癌LoVo细胞系,分别应用Hh信号通路阻断剂环巴明(cyclopamine)和Gli-1特异性阻断剂GANT61干预后,MTT法检测细胞增殖状态,流式细胞术检测其对细胞凋亡的影响,Hochest33258荧光染色观察结肠癌凋亡细胞核的形态学变化,Western blotting检测Hh信号通路主要分子Shh,PTCH,Smo和Gli-1蛋白及凋亡相关蛋白的表达。结果:环巴明或GANT61对结肠癌细胞的增殖有明显抑制作用,且呈浓度和时间依赖性,以GANT61抑制率最高。流式细胞术和Hochest33258结果显示:环巴明和GANT61能够诱导人结肠癌LoVo细胞凋亡。Western blotting结果显示,环巴明和GANT61均可抑制Gli-1蛋白的表达,下调Bcl-2蛋白的表达,上调Bax蛋白的表达。结论:Hh信号通路在结肠癌细胞中呈活化状态,通过抑制该通路,特别是特异性阻断Gli-1,可有效抑制结肠癌细胞增殖,并促进其凋亡,其机制可能是通过阻断Hh信号通路下游核转录因子Gli-1,引起Bcl-2表达下调,Bax表达上调。
关 键 词: 肿瘤学;结肠癌;Hedgehog信号通路;Gli-1;增殖;凋亡
Title: Effects and mechanisms of suppressing Hedgehog signaling pathway on proliferation in colorectal cancer cells
Author: WANG Jun, DONG Weiguo, GUO Xufeng, SONG Jia, YU Shijie, LIU Min
Organization: Key Laboratory of Hubei Province for Digestive System Disease, Department of Gastroenterology, Renmin Hospital of Wuhan University
Abstract: Objective: To explore the effect of Hedgehog (Hh) signaling pathway in colorectal cancer cells and its mechanism. Methods: Human colorectal cancer LoVo cells were selected and intervened by inhibitors cyclopamine and GANT61, respectively. The MTT colorimetry was used to detect the growth inhibitory rates, and the apoptosis potential of cells was assessed by flow cytometry. In addition, Hochest33258 fluorochrome staining was employed to observe cell apoptosis and the expressions of Hedgehog signaling related protein such as Shh, PTCH, Smo and Gli-1and apoptosis proteins were detected by Western blotting. Results: Cyclopamine and GANT61 inhibited the growth of LoVo cells in a dose- and time-dependent manner. Compared with the cyclopamine group, the inhibitory rate of GANT61 group was higher. The apoptosis rates also increased after drug intervention. Hochest33258 fluorochrome staining showed that there were many apoptosis cells in cyclopamine and GANT61 groups. The expression of Gli-1 and Bcl-2 were decreased, while the expression of Bax was increased. Conclusion: Hh signaling pathway was activated in human colorectal cancer cells. Inhibiting this pathway, especially specific blocking Gli-1, can inhibit cell proliferation and induce apoptosis, the mechanism may be that the nuclear transcription factor Gli-1 of Hh signaling pathway downstream is blocked, thus causes Bcl-2 down-regulation and Bax up-regulation.
Key words: oncology; colorectal cancer; Hedgehog signaling pathway; Gli-1; proliferation; apoptosis
发表期数: 2014年6月第11期
引用格式: 王军,董卫国,郭绪峰,等. 靶向阻断Hedgehog信号通路对结肠癌细胞增殖的影响及机制[J]. 中国科技论文在线精品论文,2014,7(11):1038-1043.
 
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