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PGE_2通过Gαs-cAMP-PKA通路上调子宫内膜癌细胞VEGF的表达 被引量:1

Increased expression of VEGF by prostaglandin E_2 through activation of Gα s-cAMP-PKA pathway in endometrial cancer cell
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摘要 目的 :探讨PGE2(prostaglandinE2,PGE2)对子宫内膜癌Ishikawa细胞血管内皮生长因子(VEGF)蛋白表达的影响及其可能涉及的信号转导通路。方法:用PGE2、4种EP受体激动剂(17-phenyltrinor prostaglandin E2、butaprost、sulprostone和prostaglandin E1 alcohol)、EP2受体拮抗剂AH6809、PKA抑制剂H89、腺苷酸环化酶(AC)抑制剂SQ22536处理Ishikawa细胞,通过Western blot实验检测VEGF蛋白表达水平的变化。结果:PGE2明显提高Ishikawa细胞VEGF蛋白的表达水平,10μmol/L PGE2处理Ishikawa细胞后,VEGF蛋白的表达水平与对照组相比升高31.56%(P<0.05);10μmol/L EP1-4受体激动剂处理Ishikawa细胞后,VEGF蛋白的表达水平与对照组相比明显增高,其中EP2受体激动剂处理组上升了87.80%(P<0.05);10μmol/L EP2受体拮抗剂AH6809处理Ishikawa细胞后,Ishikawa蛋白的表达水平较PGE2处理组下调了45.66%(P<0.05)。25μmol/L AC抑制剂SQ22536、10μmol/L PKA抑制剂H89处理Ishikawa细胞后,VEGF蛋白的表达水平较EP2受体激动剂处理组分别下降了29.00%(P<0.05)和57.50%(P<0.05)。结论:PGE2可通过EP2受体激活cAMP-PKA信号转导通路上调Ishikawa细胞VEGF蛋白的表达。 Objective:To explore VEGF expression induced by PGE2 in endometrial cancer cell and possibly involved signal transduction pathways. Methods:Ishikawa cells were treated with PGE2,EP1-4 receptor agonist,EP2 receptor antagonist AH6809,PKA inhibitor H89,and adenylate cyclase (AC) inhibitor SQ22536. Western blot was used to examine the expression of VEGF protein in Ishikawa cells cells. Results:PGE2 up-regulated the protein level of VEGF in Ishikawa cells. The level of VEGF protein was increased by 31.56%(P 〈 0.05)compared with the control group after treated with 10 μM PGE2 for 24 h. Treated with 10 μM four selective EP receptor agonists(17-phenyltrinor Prostaglandin E2,Butaprost,Sulprostone and Prostaglandin E1 Alcohol) respectivly,the protein expressions of VEGF in Ishikawa cells was increased compared with the control group. We found that EP2 receptor agonist increased the expression of VEGF protein to 87.8% (P 〈 0.05). The protein level of VEGF decreased by 45.66%(P 〈 0.05)after treated with 10 ?μM EP2 receptor antagonist compared with the group treated with PGE2. When treated with 25 μM AC inhibitor SQ22536 and 10 μM PKA antagonist H89 for 24 h,respectally,the protein levels of VEGF were decreased by 29%(P 〈 0.05)and 57.5%(P 〈 0.05)compared with the group treated with EP2 receptor agonist. Conclusion:PGE2 may up-regulate the protein expression of VEGF through EP2 receptor and Gαs-cAMP-PKA signaling pathway in Ishikawa cells.
出处 《南京医科大学学报(自然科学版)》 CAS CSCD 北大核心 2014年第5期553-556,共4页 Journal of Nanjing Medical University(Natural Sciences)
基金 国家自然科学基金(81172003) 江苏高校优势学科建设工程资助项目(JX10131801021)
关键词 PGE2 EP2受体 VEGF 子宫内膜癌 PGE2 EP2 receptor VEGF endometrial cancer
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