EP2受体介导的前列腺素E2影响胆管细胞癌细胞HuCCT1细胞间黏附因子-1表达和侵袭的研究
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国家自然科学基金(30871015, 81172003)


Prostaglandin E2 upregulates ICAM-1 expression and activity in HuCCT1 cells via the EP2 receptor signaling pathway
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    摘要:

    目的:探讨前列腺素E2(prostaglandin E2,PGE2)通过EP2受体影响人胆管细胞癌细胞HuCCT1细胞间黏附因子-1(intercellular adhesion molecule-1,ICAM-1)的表达及癌细胞的侵袭能力-方法:用PGE2-EP1~4四种受体激动剂(17-phenyltrinor Prostaglandin E2-Butaprost-Sulprostone和Prostaglandin E1 Alcohol)-EP2受体抑制剂AH6809-腺苷酸环化酶(AC)抑制剂SQ22536和蛋白激酶A(PKA)抑制剂H89处理HuCCT1细胞,通过Western blot-划痕试验等方法检测ICAM-1的蛋白表达水平以及HuCCT1细胞侵袭能力的变化-结果:PGE2明显提高HuCCT1细胞ICAM-1蛋白的表达水平,5 μmol/L PGE2处理HuCCT1细胞24 h后,ICAM-1蛋白表达水平与对照组相比上升了66.17%(P < 0.05),并呈浓度依赖性和时间依赖性;5 μmol/L PGE2处理HuCCT1细胞24 h后,HuCCT1细胞的侵袭能力较对照组增强了43.29%(P < 0.01)-10 μmol/L EP1~4受体激动剂处理HuCCT1细胞24 h后,ICAM-1蛋白的表达水平与对照组相比明显增高,其中EP2受体激动剂上升了257.88%(P < 0.05),10 μmol/L EP2受体激动剂处理HuCCT1细胞24 h后,HuCCT1细胞的侵袭能力较对照组增强了56.99%(P < 0.01);10 μmol/L EP2受体抑制剂AH6809处理后ICAM-1蛋白的表达水平与PGE2组相比下降了49.14%(P < 0.05),细胞侵袭能力下降了52.06%(P < 0.01)-25 μmol/L AC抑制剂SQ22536-10 μmol/L PKA抑制剂H89处理HuCCT1细胞后,ICAM-1蛋白的表达水平较EP2受体激动剂处理组分别下降了72.87%(P < 0.05)和80.78%(P < 0.05)-结论:PGE2可通过EP2受体激活cAMP-PKA信号转导通路上调HuCCT1细胞ICAM-1的表达,从而促进HuCCT1细胞的侵袭转移-

    Abstract:

    Objective:To investigate the effect of prostaglandin E2(PGE2) on the expression of intercellular adhesion molecule-1 (ICAM-1) and the cell migration ability by EP2 receptor in cholangiocarcinoma HuCCT1 cells. Methods: HuCCT1 cells were treated with PGE2,EP1-4 receptor agonist,EP2 receptor antagonist,AC inhibitor,and protein kinase A (PKA) inhibitor. Western blotting and scratch assay were employed to detect the protein level of ICAM-1 and the cell migration ability in HuCCT1 cells. Results: PGE2 might upregulate the protein level of ICAM-1 in cholangiocarcinoma HuCCT1 cells. The protein level of ICAM-1 was increased by 66.17%(P < 0.05) compared with the control group after treatment with 5 -滋mol/L PGE2 for 24 h,and the increase was dose- and time-dependent. The cell migration ability of HuCCT1 was increased by 43.29% (P < 0.01) compared with the group after treated with 5 -滋mol/L PGE2. The protein expression of ICAM-1 in HuCCT1 cells were increased by 257.88%(P < 0.05) after treatment with EP2 receptor agonist for 24 h,and the cell migration ability of HuCCT1 was increased by 56.99%(P < 0.01). The protein level of ICAM-1 decreased by 49.14% (P < 0.05) compared with the group,which were treated with PGE2 after treatment with 10 -滋mol/L EP2 receptor antagonist,and the cell migration ability of HuCCT1 decreased by 52.06% (P < 0.01). When treated with 25 -滋mol/L AC inhibitor SQ22536 and 10 -滋mol/L PKA antagonist H89 for 24h,the protein levels of ICAM-1 were decreased by 72.87%(P < 0.05),80.78%(P < 0.05) compared with the group treated with EP2 receptor agonist. Conclusion: PGE2 upregulates the protein level of ICAM-1 and the cell migration ability through EP2 receptor in cholangiocarcinoma HuCCT1 cells,which could be partly related to the cAMP-PKA signaling pathway.

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许 燕,白小明,张 丽,马 娟,张 海,汪亦品,冷 静. EP2受体介导的前列腺素E2影响胆管细胞癌细胞HuCCT1细胞间黏附因子-1表达和侵袭的研究[J].南京医科大学学报(自然科学版),2012,(5):592-597

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  • 收稿日期:2011-12-28
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