HMGB1通过RAGE促进肝内胆管癌细胞增殖、侵袭的机制研究
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江苏省科技厅自然科学课题(BK2012871);江苏省卫生厅课题(H201408);江苏省六大人才高峰资助计划(WSH-018)


Impact of HMGB1 and RAGE on the proliferation and invasion of human cholangiocarcinoma
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    摘要:

    目的:检测高迁徙率族蛋白1(high mobility group protein 1,HMGB1)及其受体晚期糖基化终末产物受体(receptor for advanced glycation end-products,RAGE)在肝内胆管癌组织中的表达;探讨HMGB1/RAGE对肝内胆管癌细胞增殖及上皮-间质细胞转化(epithelial-mesenchymal transition,EMT)过程中的作用。方法:免疫组化分析未转移和已转移胆管癌患者标本中HMGB1及RAGE的表达;ELISA法检测胆管癌及胆管结石患者胆汁中HMGB1的含量;CCK8-Transwell检测HMGB1及RAGE抑制剂(FFP-ZM1)对胆管癌细胞增殖-侵袭作用的影响;Western blot检测胆管癌及癌旁组织中p-ERK的表达。结果:HMGB1和RAGE在已转移的胆管癌患者组织标本中高表达,HMGB1可促进胆管癌细胞的EMT过程及胆管癌细胞的生长和侵袭。结论:HMGB1可参与胆管癌细胞的增殖与EMT过程。

    Abstract:

    Objective: To detect the expression of high mobility group protein 1 (HMGB1) and the receptor for advanced glycation end products (RAGE) in the tissues of patients suffering from cholangiocarcinoma, and to study the possible mechanism of HMGB1 and RAGE on the growth and epithelial-mesenchymal transition (EMT) of human cholangiocarcinoma cells. Methods:Immunhistochemical study was performed to analyze the expression of HMGB1 and RAGE in cholangiocarcinoma tissues with or without metastasis; ELISA method was used to detect the level of HMGB1 in the bile of patients with hepatolithiasis and cholangio-carcinoma;The effect of HMGB1 and RAGE on cell proliferation and invasion was detected by CCK8 and Transwell assay; the expression of HMGB1 and p-ERK in tissues of cholangiocarcinoma was detected by Western blot. Results: HMGB1 and RAGE were significantly higher in cholangiocarcinoma tissues with metastasis than in those without metastasis. HMGB1/RAGE can obviously promote the growth of cholangiocarcinoma cell line in vitro and promote the expression of EMT relative cytokines. Conclusion: HMGB1 and RAGE can promote the EMT and proliferation of cholangiocarcinoma cell line

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聂俊杰,尤 强,葛贤秀,李全朋,王 飞,许伯明,张秀华,季国忠,缪 林. HMGB1通过RAGE促进肝内胆管癌细胞增殖、侵袭的机制研究[J].南京医科大学学报(自然科学版),2016,(9):1025-1030

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  • 收稿日期:2016-04-13
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  • 在线发布日期: 2016-09-18
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