中国药理学通报2016，Vol.32Issue(7)：925-931,932,8.DOI:10.3969/j.issn.1001-1978.2016.07.009
熊果酸抑制胃癌细胞 COX-2表达的信号转导研究
Signal transduction pathway of ursolic acid inhibiting COX-2 expression in gastric cancer cells
摘要
Abstract
Aim Our previous study has found that ur-solic acid( UA) increased intracellular reactive oxygen species ( ROS ) production and adenosine monophos-phate-activated protein kinase ( AMPK ) phosphoryla-tion, inhibited signal transducer and activator of tran-scription 3 ( STAT3 ) phosphorylation and cyclooxygen-ase-2 ( COX-2 ) expression in gastric cancer cells . However , the molecular mechanism by which UA in-hibits COX-2 expression in gastric cancer cells has not been fully clarified .In this study we aimed to further clarify the signal transduction pathways involved in the UA-mediated inhibition of COX-2 expression in gastric cancer cells .Methods Human gastric cancer cell lines SGC-7901 and MKN-45 were routinely cultured in RPMI-1640 medium supplemented with 10% heat-in-activated fetal calf serum .Sub-confluent cell cultures were pre-treated with antioxidant N-acetylcysteine ( NAC) , AMPK activator 5-amino-4-imida-zolecarbox-amide-riboside ( AICAR ) , AMPK inhibitor compound C, or STAT3 inhibitor WP1066 and then treated with or without UA for 24 h.The expression of AMPK and phosphorylated AMPK ( p-AMPK ) , STAT3 and phos-phorylated STAT3 ( p-STAT3 ) , as well as COX-2 was detected by Western blot analysis .Results Antioxi-dant NAC and AMPK inhibitor compound C blocked UA-induced inhibition of STAT 3 phosphorylation and down-regulation of COX-2 expression in gastric cancer cells.Both AMPK activator AICAR and UA inhibited STAT3 phosphorylation and COX-2 expression; the combination of two drugs resulted in further reduction . STAT3 inhibitor WP1066 did not affect UA-induced AMPK phosphorylation , whereas it inhibited STAT3 phosphorylation and COX-2 expression .The inhibitory effects on the STAT3 phosphorylation and COX-2 ex-pression were significantly enhanced when SGC-7901 and MKN-45 cells were treated simultaneously with WP1066 plus UA.Conclusion UA inhibits COX-2 expression in gastric cancer cells , which may be medi-ated through ROS/AMPK/STAT3 signal transduction pathway .关键词
熊果酸/胃癌/活性氧/单磷酸腺苷激活的蛋白激酶/信号转导与转录活化因子3/环氧化酶-2Key words
ursolic acid/gastric cancer/reactive oxy-gen species/adenosine monophosphate-activated pro-tein kinase/signal transducer and activator of tran-scription 3/cyclooxygenase-2分类
医药卫生引用本文复制引用
朱悦,周逸婵,朱国琴,李剑萍,焦政,李晓林,邵耘,孙为豪..熊果酸抑制胃癌细胞 COX-2表达的信号转导研究[J].中国药理学通报,2016,32(7):925-931,932,8.基金项目
国家自然科学基金面上项目 （）
