去氢骆驼蓬碱通过PTEN/Akt/MDM2信号通路抑制胃癌细胞COX-2表达  

Harmine inhibits COX-2 expression in gastric cancer cells through PTEN/Akt/MDM2 signaling pathway

作　　者：陶婷婷[1] 蒋世烨 孙梦雪 张文灵 余纳 刘高双[1] 李晓林[1] 邵耘[1] 孙为豪[1] TAO Ting-ting;JIANG Shi-ye;SUN Meng-xue;ZHANG Wen-ling;YU Na;LIU Gao-shuang;LI Xiao-lin;SHAO Yun;SUN Wei-hao(Dept of Geriatric Gastroenterology,the First Affiliated Hospital of Nanjing Medical University,Nanjing210029,China)

机构地区：[1]南京医科大学第一附属医院老年消化科,江苏南京210029

出　　处：《中国药理学通报》2019年第5期695-700,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81372659)

摘　　要：目的探讨PTEN基因/Akt/小鼠双微体基因(MDM2)信号通路在去氢骆驼蓬碱(harmine,HM)抑制胃癌细胞COX-2表达中的作用。方法构建PTEN(PTEN-siRNA)、Akt(Akt-siRNA)和MDM2(MDM2-siRNA)小干扰RNA,分别转染胃癌细胞株SGC-7901和MKN-45,Western blot检测HM干预前后PTEN、p-Akt、p-MDM2和COX-2表达。结果 HM诱导PTEN表达,抑制Akt、MDM2磷酸化和COX-2表达。敲减PTEN基因有效地阻断了HM抑制Akt、MDM2磷酸化和COX-2表达的作用,敲减Akt基因可协同HM抑制MDM2磷酸化和COX-2表达,敲减MDM2基因可协同HM抑制COX-2表达。结论 HM可能通过PTEN/Akt/MDM2信号通路,下调胃癌细胞COX-2表达。Aim To further analyze the effects of PTEN/Akt/MDM2 signaling pathway in the harmine (HM)-mediated inhibition of COX-2 expression in gastric cancer cells. Methods PTEN-siRNA,Akt-siRNA,MDM2-siRNA were constructed and respectively transfected into SGC-7901 and MKN-45 cells,and then added or not added HM for 24 h.The expression of PTEN,Akt and phosphorylated Akt (p-Akt),MDM2 and phosphorylated MDM2 (p-MDM2),as well as COX-2 expression was detected by Western blot. Results HM increased PTEN expression,but inhibited p-Akt,p-MDM2 and COX-2 expression in SGC-7901 and MKN-45 cells.Knockdown of PTEN blocked HM-induced inhibition of Akt and MDM2 phosphorylation,as well as down-regulation of COX-2 expression.Knockdown of Akt and treatment with HM synergistically inhibited p-MDM2 and COX-2 expression.Knockdown of MDM2 and treatment with HM synergistically inhibited COX-2 protein expression. Conclusions HM down-regulates the expression of COX-2 protein in gastric cancer cells via PTEN/Akt /MDM2 signaling pathway.

关 键 词：去氢骆驼蓬碱 胃癌 PTEN基因 AKT 小鼠双微体基因 环氧合酶2 

分 类 号：R-332[医药卫生] R284.1