特异性阻断Shh信号通路对胰腺癌细胞系SUIT-2增殖和凋亡的影响
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胡伟国

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Effect of sonic hedgehog signal pathway blocking on the proliferation and apoptosis of pancreatic cancer cell line SUIT-2
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    摘要:

    目的: 研究组抑胚胎发育相关信号通路Sonic hedgehog (Shh)对人胰腺癌细胞系SUIT-2增殖和凋亡的影响。方法:用四唑蓝(MTT)比色试验检测Shh信号通路特异性抑制剂cyclopamine对胰腺癌细胞系SUIT-2增殖的抑制作用;流式细胞术检测细胞增殖指数(PI)和凋亡指数(AI);用裸鼠移植瘤模型检测cyclopamine对移植瘤生长的抑制作用。 结果:cyclopamine对SUIT-2细胞株增殖的抑制作用呈剂量和时间依赖性。cyclopamine作用后使胰腺癌细胞周期阻滞在G0/G1期,细胞凋亡增加;SUIT-2的AI为14.3±0.35, PI为36.1±0.44,对照组分别为1.3±0.24和52.3±0.28(均P<0.05)。在裸鼠移植瘤模型中,cyclopamine同时给药组肿瘤生长明显受到抑制,而延期给药组对肿瘤生长的抑制作用较弱。结论:shh信号分子对胰腺癌细胞的增殖起维持作用;通过特异性阻断该信号通路,可以抑制胰腺癌细胞增殖,并促进细胞凋亡。

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    Abstract:Objective:To investigate the effect and mechanism of cyclopamine,the inhibitor of Sonic hedgehog signaling pathway, on the proliferation and apoptosis of pancreatic cancer cell line SUIT-2. Methods:The SUIT-2 cells used in the experiment were cultured in vitro,and the MTT assay was used to examine the antiproliferative effect of cyclopamine. Flow cytometry(FCM) was used to examine the effects of cyclopamine on the proliferation index(PI) and apoptosis index(AI) of SUIT-2 cells. Nude mice tumor graft model was used to determine the effect of cyclopamine on growth inhibition of tumor graft.Results:Cyclopamine produced time and concentration dependent antiproliferative effects on SUIT-2 cells. Cyclopamine could induce apoptosis and block cell cycle at G0/G1 phase. In cyclopamin treated SUIT-2 cells, the apoptosis index(AI) was 14.3±0.35, and proliferation index(PI) was 36.1±0.44; and in control group, the AI was 1.3±0.24, the PI was 52.3±0.28(all P<0.05).In the nude mice model, cyclopamine produced apparent antiproliferative effect in concurrent treatment group, but had weaker effect in delayed treatment group. Conclusions:shh signaling pathway is essential for the maintaining of pancreatic cancer cell proliferation. Blocking shh pathway can inhibit the growth of pancreatic cancer cell and induce apoptosis.

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胡伟国,王春友,刘涛,赵刚.特异性阻断Shh信号通路对胰腺癌细胞系SUIT-2增殖和凋亡的影响[J].中国普通外科杂志,2006,15(6):6-418.
DOI:10.7659/j. issn.1005-6947.2006.06.006

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  • 在线发布日期: 2006-06-25