文章摘要
黄文勇,张 丽,束 为,彭 韬,张 海,马 娟,白小明,冷 静.PGE2通过EP2受体激活cAMP-PKA-CREB信号通路上调SnoN的表达而促进CCLP1细胞的增殖[J].南京医科大学学报,2011,(2):143~148
PGE2通过EP2受体激活cAMP-PKA-CREB信号通路上调SnoN的表达而促进CCLP1细胞的增殖
Prostaglandin E2 promotes the cell prolifelation ability of CCLP1 through EP2 prostanoid receptor which increased the expression of SnoN by activation of cAMP-PKA-CREB pathway
投稿时间:2010-10-20  
DOI:10.7655
中文关键词: 胆管上皮癌  PGE2  EP2受体  SnoN  cAMP-PKA-CREB
英文关键词: bile duct carcinoma  PGE2  EP prostanoid receptor  SnoN  cAMP-PKA-CREB
基金项目:国家自然科学基金(30470784,30871015)
作者单位
黄文勇 南京医科大学病理学系,肿瘤中心,生殖医学重点实验室,江苏 南京 210029 
张 丽 南京医科大学病理学系,肿瘤中心,生殖医学重点实验室,江苏 南京 210029 
束 为 南京医科大学附属口腔医院牙周科,口腔医学研究所,江苏 南京 210029 
彭 韬 南京医科大学病理学系,肿瘤中心,生殖医学重点实验室,江苏 南京 210029 
张 海 南京医科大学病理学系,肿瘤中心,生殖医学重点实验室,江苏 南京 210029 
马 娟 南京医科大学病理学系,肿瘤中心,生殖医学重点实验室,江苏 南京 210029 
白小明 南京医科大学病理学系,肿瘤中心,生殖医学重点实验室,江苏 南京 210029 
冷 静 南京医科大学病理学系,肿瘤中心,生殖医学重点实验室,江苏 南京 210029 
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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:10 μmol/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);10 μmol/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%;10 μmol/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500 μmol/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%,20 μmol/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.
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