PGE_2诱导人胃癌BGC-823细胞HIF-1α、VEGF表达的信号转导途径研究  

Study of the signal transduction pathways by whichprostaglandin E_2 inducing the expression of HIF-1αand VEGF protein in human gastric cancer cell lineBGC-823 cells

作　　者：冯玉光[1] 李建生[1] 张金平[1] 宗红[1] 陈香宇[1] 王勇[1] 

机构地区：[1]郑州大学第一附属医院,河南郑州450052

出　　处：《山东医药》2005年第31期8-10,共3页Shandong Medical Journal

基　　金：河南省医学科技创新人才工程资助课题项目(2003034);河南省教育厅自然科学研究项目(2004320009)

摘　　要：目的研究前列腺素E2(PGE2)诱导人胃癌细胞株(BGC-823)、低氧诱导因子-1α(H IF-1α)、血管内皮生长因子(VEGF)表达的信号转导途径。方法应用100μm ol/L的PGE2联合不同浓度的MAPK阻滞剂PD 98059(10、50和100μm ol/L)或磷酸肌醇3-激酶(P I3K)阻滞剂W ortm ann in(50、100和200nm ol/L)作用于BGC-823细胞24 h,收集细胞,行W estern b lot检测H IF-1α、VEGF的表达。结果正常对照组BGC-823细胞低度表达H IF-1α、VEGF蛋白,100μm ol/L PGE2刺激细胞24h显著诱导H IF-1α、VEGF蛋白表达。PD 98059或W ortm ann in均对PGE2诱导的H IF-1α和VEGF蛋白表达产生剂量依赖性抑制,100μm ol/L PD 98059几乎全部阻断了PGE2对H IF-1α和VEGF蛋白表达的诱导(P<0.01),而200nm ol/L W ortm ann in可部分阻断PGE2的这种作用。结论PGE2可能通过激活MAPK和/(或)P I3K信号转导途径调控H IF-1α蛋白表达,进而促进VEGF表达。Objective： To study the signal transduction pathways by which prostaglandin E2 （PGE2） inducing the expression of hypoxia-inducible factor-1α （HIF-1α） and vascular endothelial growth factor （VEGF） protein in cell line BGC-823 cells of human gastric cancer. Methods： BGC-823 cells simulated by 100μmol/L PGE2 combined different concentration of mitogen activated proteinkinase （MAPK） inhibitor PD98059 （10-100μmol/ L ） or phosphatidy l-inositol 3 kinase （PI3K） inhibitor Wortmannin （50-200nmol/L） for 24h and the cells were harvested, and Western blot was used to investigate the influence of PGE2 on the expression of HIF-1α and VEGF in the cell line. Results： Western blot analysis demonstrated that HIF-1α protein was weakly or negatively expressed while basal VEGF protein levels were found in BGC-823 cells under normoxic conditions, 100μmol/L PGE2 significantly induced the expression of HIF-1α and VEGF protein in normoxic cells at 24h, PD98059 or Wortmannin both significantly suppressed PGE2-induced up-regulation of HIF-1α and VEGF protein expression in a dose-dependent fashion. 100μmol/L PD98059 almost completely inhibited PGE2-induced upregulation of HIF-1α and VEGF protein expression, while 200nmol/L Wortmannin also partly blocked PGE2- induced HIF-1α and VEGF protein expression. Conclusion： PGE2 induces HIF-1α and HIF-1-mediated VEGF expression, which is dependent on MAPK and PI3K signaling in BGC-823 cells.

关 键 词：胃癌细胞株 前列腺素E2 低氧诱导因子-1Α 血管内皮生长因子 

分 类 号：R571[医药卫生—消化系统]