吲哚美辛通过Akt/GSK3β/NAG-1信号通路诱导胃癌细胞的凋亡  

Indomethacin induces gastric cancer cell apoptosis through Akt/GSK3β/NAG-1 pathway

作　　者：庞瑞萍[1] 胡品津[2] 曾志荣[2] 陈为[2] 

机构地区：[1]中山大学中山医学院生理教研室,广东广州510080 [2]中山大学第一附属医院消化内科,广东广州510080

出　　处：《中国病理生理杂志》2011年第8期1513-1518,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30800336);广东省自然科学基金资助项目(No.8151008901000009);中山大学医科青年教师科研启动基金资助项目(No.2007002)

摘　　要：目的:探讨非选择性环氧合酶抑制剂吲哚美辛诱导胃癌细胞凋亡作用与Akt/GSK3β/NAG-1信号通路的关系。方法:MTT法测定胃癌细胞的活力;Hoechst 33258染色检测细胞形态学改变,流式细胞术检测DNA含量的变化,Western blotting检测蛋白表达的变化。结果:吲哚美辛通过caspase通路诱导胃癌细胞MGC-803的凋亡,明显降低Akt和GSK3β的磷酸化水平,同时上调NAG-1的表达。单独抑制PI3K或Akt的活性亦可上调NAG-1的表达,而GSK3β抑制剂预处理后则取消吲哚美辛上调NAG-1表达的作用。结论:吲哚美辛可通过Akt/GSK3β/NAG-1信号通路诱导胃癌细胞MGC-803的凋亡。AIM： To investigate whether indomethacin induces gastric cancer cell apeptosis through Akt/ GSK3β/NAG- 1 pathway. METHODS： Gastric cancer cell line MGC- 803 was used in the study. Cell viability was measured by MTT method. Hoechst 33258 nuclear staining and flow cytometry analysis were used to determine apeptosis. The protein expression level was examined by Western blotting. RESULTS： Indomethaein induced MGC -803 cell apeptosis via caspase - dependent pathway. Indomethacin inhibited Sef,473 - Akt and Set9 - GSK3β phosphorylation and up - regulated the expression of non - steroidal anti - inflammatory drug - activated gene - 1 （ NAG - 1 ）. Inhibition of PI3K or Akt alone also increased NAG - 1 expression. Moreover, the effect of indomethacin on NAG - 1 expression was abolished by pretreatment of the cells with GSK3β inhibitor SB216763. CONCLUSION： Indomethacin induces gastric cancer call apeptosis through Akt/GSK3β/NAG- 1 pathway.

关 键 词：吲哚美辛 环氧合酶 MGC-803细胞 细胞凋亡 Akt/GSK3β/NAG-1通路 

分 类 号：R735.2[医药卫生—肿瘤]