NK4抑制结肠癌细胞增殖的机制初探
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张辉

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Premliminary study of NK4 inhibition on proliferation of colon cancer cells
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    摘要:

    目的:探讨肝细胞生长因子及其受体(HGF/cMet)拮抗剂对结肠癌细胞的作用及其与MEK/ERK信号通路的关系,明确以HGF/cMet为靶点治疗结肠癌的细胞内信号传导机制。方法:分别将HGF及选择性cMet拮抗剂NK4作用于结肠癌细胞系LoVo,运用MTT法分别于0,6,12,24h检测细胞增殖状态;流式细胞仪观察两者对细胞凋亡的影响。采用Western blot检测药物作用前后cMet,pcMet,MEK2和pERK及其靶基因产物Cmyc的表达。结果:NK4组呈剂量依赖性方式抑制结肠癌细胞增殖,促进其凋亡,并使pcMet及MEK2/ERK通路相关蛋白表达下调,而HGF组则使其表达上调;同时处理24h后,空白组 与NK4组(1μg/mL)中pcMet,MEK2,pERK及Cmyc蛋白表达水平比值分别为2.58,1.89,1.67和2.21(P<0.01),而与HGF(50ng/mL)组相关蛋白比值为0.46,0.71,068和0.58(P<0.01)。结论:选择性HGF拮抗剂NK4抗结肠癌可能通过阻断MEK2/ERK信号传导通路影响肿瘤细胞增殖与凋亡,以HGF/cMet为靶点的结肠癌信号通路阻断治疗具有可行性和有效性 。

    Abstract:

    ObjectiveTo investigate the influence of selective HGF/cMet inhibitorNK4 against colon cancerand reveal the potential signaling pathway mechanism of NK4 effect on colon cancer cell. MethodsLoVo colon cancer cells were treated with NK4(a selective inhibitor of cMet phosphorylation)at different times. MTT assay and flow cytometry were used to measure cell proliferation and apoptosis. The expression of cMet, pcMet, MEK2, pERK and Cmyc were measured by Western blot. ResultsIn NK4treated group, cells proliferation were inhibited and apoptosis induced in a dose dependent manner, and resulted in significantdownregulation of pcMet and MEK2/ERK pathwayrelated protein. The effect of HGF/on LoVo was the opposite. The ratios of pcMet, MEK2, pERK and Cmyc expression between blank group and the NK4(1μg/mL)treated for 24h group were 2.58, 1.89, 1.67 and 2.21(P<0.01), and for HGF(50mg/mL) group were 0.46, 0.71, 068, 0.58(P<0.01), respectively. ConclusionsThe results showed that selective cMet inhibitor NK4 may inhibit proliferation and induce apoptosis of colon cancer cell lines LoVo through blockade of MEK2/ERK signaling pathway. It may be a new target of selective HGF/cMet inhibitor effect on colon cancer.

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李静喆,张辉,张仲良,张永清,李其棠. NK4抑制结肠癌细胞增殖的机制初探[J].中国普通外科杂志,2005,14(10):9-747.
DOI:10.7659/j. issn.1005-6947.2005.10.009

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  • 在线发布日期: 2005-10-25