表皮生长因子受体抑制剂AG1478影响HuH7细胞黏附、迁移和侵袭的研究
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国家自然科学基金资助项目(30470784);江苏省生殖医学重点实验室开放课题资助项目(07SZKF09);江苏省高校自然科学研究项目(05KJB310081)


The effect of EGFR signal transduction pathway on the adhesion migration and invasion of human hepatocellular carcinoma
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    目的:研究表皮生长因子受体(epidermal growth factor receptor,EGFR)抑制剂AG1478对人肝细胞癌细胞HuH7黏附、迁移及侵袭的影响及其相关细胞内信号转导通路,探讨EGFR在肿瘤转移中的作用。方法:用AG1478处理人肝细胞癌细胞HuH7;用MTT法检测细胞的黏附能力变化;用Transwell小室观察体外细胞迁移能力变化;Transwell小室结合Matrix胶检测肿瘤细胞侵袭能力的变化;用Western blot法检测Erk2及Paxillin蛋白表达。结果:AG1478(20 μmol/L)处理后,细胞的黏附、迁移和侵袭能力分别下降了52%、49%和70%(P < 0.01),Erk2及Paxillin的表达水平也明显降低(P < 0.01)。结论:EGFR与人肝细胞癌细胞HuH7的黏附、迁移和侵袭性密切相关,并可能通过Erk2及Paxillin信号转导通路调控人肝细胞癌的发展。

    Abstract:

    Objective:To investigate the effect of epidermal growth factor receptor(EGFR) inhibitor AG1478 on adhesion,migration and invasion of HuH7 cell line and its molecular mechanism. Methods:HuH7 cells were treated with AG1478. Cell adhesion assay and Matrix-gel were used to examine the capability of adhesion,migration and invasion. Western blotting was employed to detect the expression of Erk2 and Paxillin in HuH7 cells. Results:AG1478(20 μmol/L) significantly inhibited the adhesion of HuH7 cells by 52%. And Matrix-gel experiment showed that AG1478(20 μmol/L) decreased the migration and invasion ability of HuH7 cells in vitro by 49% and 70%,respectively(P < 0.01). After the treatment of AG1478 for 24 h,the expression of Erk2 and Paxillin were decreased remarkably(P < 0.01). Conclusion:Our findings suggested that EGFR signal transduction pathway might play a key role on the capability of adhesion,migration and invasion in human HCC cell line HuH7,which could be partly related to the mechanism of Erk2 and Paxillin signal pathway.

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张 玮,白小明,冷 静.表皮生长因子受体抑制剂AG1478影响HuH7细胞黏附、迁移和侵袭的研究[J].南京医科大学学报(自然科学版),2008,28(4):424-428

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  • 收稿日期:2007-11-20
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