醌茜素通过MAPK及Akt信号途径诱导人胃癌AGS细胞凋亡  

Quinalizarin induces apoptosis in gastric cancer AGS cells via MAPK and Akt signaling pathway

作　　者：刘畅[1] 罗英花[2] 朴仙姬 王玥[1] 孟令旗[1] 王浩[1] 王加茹 张翼[1] 李金钱 金成浩[1] 

机构地区：[1]黑龙江八一农垦大学生命科学技术学院,黑龙江大庆163319 [2]黑龙江八一农垦大学动物科学技术学院,黑龙江大庆163319 [3]哈尔滨医科大学第五医院,黑龙江大庆163316

出　　处：《南方医科大学学报》2017年第8期1085-1091,共7页Journal of Southern Medical University

基　　金：黑龙江八一农垦大学研究生创新科研项目(YJSCX2017-Y72);黑龙江省自然基金(LC2015036);学成;引进人才科研启动计划项目(XYB2013-24)

摘　　要：目的探讨醌茜素对人胃癌细胞的凋亡作用及其分子机制。方法 MTT法检测醌茜素对3种人胃癌AGS、MKN-28及MKN-45细胞的杀伤作用;Annexin V-FITC/PI双染法、流式细胞术检测醌茜素诱导AGS细胞凋亡能力及细胞内活性氧簇(ROS)水平;蛋白质免疫印迹法检测细胞凋亡相关蛋白的表达量变化。结果醌茜素对3种胃癌细胞均具有明显的杀伤作用,且呈浓度依赖性(P<0.05)。经计算其IC50值分别为7.07μmol/L、22.55μmol/L及14.18μmol/L。醌茜素能诱导AGS细胞发生凋亡,且呈浓度依赖性(P<0.001),并能够促进细胞内活性氧水平升高(P<0.001)。当预处理ROS清除剂NAC后,能够明显抑制醌茜素诱导的细胞凋亡(P<0.001)。Western blotting结果显示促凋亡蛋白p-p38、p-JNK、Bad、cleaved-caspase-3及cleaved-PARP-1表达量增加(P<0.05),抗凋亡蛋白p-Akt、p-ERK及Bcl-2蛋白表达量减小(P<0.05)。结论醌茜素通过上调细胞内ROS水平,调控MAPK及Akt信号途径,进而诱导人胃癌AGS细胞发生凋亡。Objective To investigate quinalizarin-induced apoptosis in gastric cancer cells in vitro and explore the molecular mechanisms. Methods MTT assay was used to determine the cytotoxic effects of quinalizarin on human gastric cancer AGS, MKN-28 and MKN-45 cells. Annexin V-FITC/PI staining and flow cytometry were used to assess quinalizarin-induced apoptosis in AGS cells and its effect on intracellular ROS levels; the expression levels of apoptotic proteins in the cells were determined with Western blotting. Results Quinalizarin dose-dependently reduced the cell viabilities of the 3 gastric cancer cells （P〈0.05）. The IC50 values of quinalizarin in AGS, MKN-28 and MKN-45 cells were 7.07 μmol/L, 22.55 μmol/L and 14.18μmol/L, respectively. Quinalizarin time-dependently induced apoptosis of AGS cells and potentiated the generation of intracellular reactive oxygen species （ROS） levels. Pretreatment with NAC, a scavenger of ROS, inhibited quinalizarin-induced apoptosis （P〈0.001）. Western blotting results showed that quinalizarin also up-regulated the expression levels of the apoptotic proteins including p-p38, p-JNK, Bad, cleaved caspase-3, and cleaved PARP-1 （P〈0.05）, and down-regulated the expression of the anti-apoptotic proteins p-Akt, p-ERK, and Bcl-2 （P〈0.05）. Conclusion Quinalizarin inhibits the proliferation and induces apoptosis in gastric cancer cells in vitro through regulating intracellular ROS levels via the MAPK and Akt signaling pathways.

关 键 词：醌茜素 人胃癌细胞 细胞凋亡 活性氧簇 信号途径 

分 类 号：R96[医药卫生—药理学]