中文摘要：

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-phenyltrinorProstaglandin 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,5μmol/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;5μmol/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）。10μmol/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）,10μmol/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）;10μmol/LEP2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）。25μmol/L AC抑制剂SQ22536、10μmol/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。

英文摘要：

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 choiangiocarcinoma 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 txmol/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 μmol/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 I- CAM-1 decreased by 49.14% （P 〈 0.05） compared with the group,which were treated with PGE2 after treatment with 10 μmol/L EP2 receptor antagonist,and the cell migration ability of HuCCT1 decreased by 52.06% （P 〈 0.01）. When treated with 25 μmol/L AC inhibitor SQ22536 and 10 μmol/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 HnCCT1 cells,which could be partly related to the cAMP-PKA signaling pathway.