前列腺素E2对人肝癌细胞β1-integrin表达调控及相关机制的研究  

The role of PGE2 on β1-integrin expression and its related mechanism in hepatocellular carcinoma

作　　者：王洁[1] 白小明[1] 张海[1] 汪亦品[1] 张丽[1] 马娟[1] 冷静[1] 

机构地区：[1]南京医科大学肿瘤中心,生殖医学重点实验室,病理学系,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2013年第3期297-302,共6页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金(81172003,81101496);教育部高等学校博士学科点专项科研基金(20113234120009);江苏高校优势学科建设工程项目(JX10131801021)

摘　　要：目的:阐明前列腺素E2(prostaglandin E2,PGE2)通过EP1受体上调肝癌细胞Huh-7中β1-integrin的表达及其相关的信号转导通路。方法:用PGE2、EP1受体激动剂(17-PT-PGE2)、EP1受体抑制剂SC19220、NF-κB抑制剂PDTC处理Huh-7细胞,通过Western blot、免疫荧光组织化学实验等方法检测β1-integrin蛋白表达水平和NF-κB的活性。结果:5μmol/L的PGE2处理Huh-7细胞24 h后,β1-integrin的表达水平与对照组相比上升了129.48%(P<0.01),5μmol/L EP1受体激动剂17-PT-PGE2处理使细胞β1-integrin的蛋白表达水平升高了216.34%(P<0.01)。10μmol/L的EP1受体抑制剂SC19220处理后β1-integrin表达水平与PGE2组相比下降了34.51%(P<0.05)。免疫荧光组织化学实验显示17-PT-PGE2处理Huh-7细胞120 min后,NF-κB核表达水平明显增加;Western blot实验显示5μmol/L 17-PT-PGE2处理Huh-7细胞120 min后,磷酸化NF-κB-p65上升了209.27%(P<0.01)。NF-κB抑制剂PDTC处理Huh-7细胞后β1-integrin蛋白表达水平与EP1受体激动剂组相比降低了63.49%(P<0.01)。结论:PGE2可通过EP1受体上调Huh-7细胞中β1-integrin的表达,此调节作用可能与NF-κB信号转导通路有关。Objective：To investigate the effect of prostaglandin E2 （PGE2） on the expression of β1-integrin and its related signaling pathway in Huh-7 cells. Methods：Huh-7 cells were treated with PGE2,EP1 receptor agonist（17-phenyhrinor Prostaglandin E2,17-PT- PGE2）, EP1 receptor antagonist SC19220,nuclear factor-KappaB （NF-KB）inhibitor PDTC. Western blot and immunofluorescence test were employed to detect the expression of β1-integrin and activation of NF-KB in Huh-7 cells. Results：When Huh-7 cells were treated with 5 Ixmol/L PGE2 for 24 h,the level of β1-integrin was increased by 129.48% （P 〈 0.01）. EP1 receptor agonist （5 μmol/L 17-PT-PGE2） mimicked the effect of PGE2, and increased the expression of β1-integrin by 216.34% （P 〈 0.01）. EP1 receptor antagonist SC19220 （10 μmol/L） suppressed PGE2-mediated expression of β1-integrin by 34.51% （P 〈 0.05）. In immunofluorescence assays, NF-KB translocated into the nucleus induced by 17-PT-PGE： in Huh-7 cells. Further,Western blot assays showed that the level of Phospho-NF-KB-P65 was increased by 209.27% （P 〈 0.01 ）after treatment of 5 p, mol/L 17-PT-PGE2 for 120 min. NF-KB inhibitor PDTC decreased EPl-mediated expression of 131-integrin by 63.49% （P 〈 0.01）. Conclusion：PGE2 might up-regulate the expression level of β 1-integrin through EP1 receptor in Huh-7 cells, which was partly related to the NF-KB signaling pathway.

关 键 词：前列腺素E2 EP1受体 Β1-INTEGRIN NF-ΚB 

分 类 号：R735.7[医药卫生—肿瘤]