中文摘要：

目的：探讨前列腺素E2（prostaglandin E2,PGE2）对人胆管上皮癌细胞CCLP1增殖能力影响的作用机制。方法：用PGE2、EP1～4 4种受体激动剂、AC激动剂Forskolin、PKA抑制剂H89、cAMP拟似物db-cAMP处理CCLP1细胞,通过RT-PCR、Western blot、WST等实验检测SnoN mRNA、SnoN蛋白等表达水平、CREB蛋白磷酸化水平以及CCLP1细胞增殖能力的变化。结果：10μmol/L PGE2处理CCLP1细胞24 h后,SnoN mRNA的表达水平与对照组相比上升了22.5%（P〈0.01）,SnoN蛋白的表达水平上升了35.6%（P〈0.05）;10μmol/L EP受体激动剂处理CCLP1细胞24 h后,SnoN蛋白的表达水平与对照组相比明显增高,其中以EP2受体激动剂的作用最明显,上升了64.9%（P〈0.05）,细胞增殖能力上升了26.5%;10μmol/L AC激动剂Forskolin处理CCLP1细胞24 h后,SnoN蛋白的表达水平及CREB蛋白的磷酸化水平较对照组分别上升了25.1%、71.3%（P〈0.05）,细胞增殖能力也上升了4.4%（P〈0.05）;用500μmol/L cAMP拟似物dbcAMP处理CCLP1细胞24 h后,SnoN蛋白的表达水平较对照组上升了90.1%（P〈0.05）;而PKA抑制剂H89阻断Forskolin的作用后,SnoN蛋白的表达水平和CREB蛋白的磷酸化水平较Forskolin处理组分别下降了9.1%、14.1%,20μmol/L H89处理CCLP1细胞后,细胞增殖能力较对照组下降了45.7%（P〈0.05）。结论：PGE2可通过EP2受体激活cAMP-PKA-CREB信号转导通路上调CCLP1细胞SnoN的表达,从而促进CCLP1细胞的增殖。

英文摘要：

Objective： To explore the mechanism of prostaglandin E2（PGE2）affects the cell proliferation ability of human bile duct carcinoma cells CCLP1.Methods：CCLP1 cells were treated with PGE2,EP1-4 receptor agonist,AC agonist（Forskolin）,PKA antagonist（H89）,cAMP analogues（db-cAMP）.The expression levels of SnoN mRNA and SnoN protein,and the cell proliferation ability were examined by RT-PCR,Western blot and WST methods in CCLP1 cells.Results：The expression of SnoN mRNA in CCLP1 cells increased by 22.5%（P 〈 0.01）,while the level of snoN protein increased by 35.6%（P 〈 0.05）after treated with 10 μmol/L PGE2 for 24 h;The expression of SnoN protein in CCLP1 cells increased by 64.9%（P 〈 0.05）after treated with EP2 receptor agonist（10 μmol/L）for 24 h,and cell proliferation ability of CCLP1 increased by 26.5%;The levels of SnoN protein and CREB phosphorylation in CCLP1 cells increased by 25.1% and 71.3%（P 〈 0.05）respectively compared with the control group after treated with AC agonist Forskolin（10 μmol/L）for 24 h,and cell proliferation ability of CCLP1 increased by 4.4%（P 〈 0.05）after treated with 10 μmol/L Forskolin;The expression of SnoN in CCLP1 cells increased by 90.1%（P 〈 0.05）when treated with cAMP analogues db-cAMP（500 μmol/L）for 24 h,and decreased when treated with PKA antagonist H89（10 μmol/L）for 24 h,the levels of SnoN expression and CREB phosphorylation in CCLP1 cells treated with H89 decreased by 9.1% and 14.1%（P 〈 0.05）compared with those treated with Forskolin.Cell prolifelation of CCLP1 decreased by 45.7%（P 〈 0.05）after treated with 20 μmol/L H89.Conclusion：PGE2 might up-regulate the expression level of SnoN through EP2 receptor of CCLP1 cells which could be partly related to the cAMP-PKA-CREB signaling pathway,and promote the cell proliferation.