水飞蓟素可通过MAPK信号转导通路促进肺腺癌A549细胞凋亡  

Apoptosis of lung adenocarcinoma cell Line A549 promoted by silymarin through MAPK signal transduction pathway

作　　者：李文海[1] 梁军[2] 王春梅[3] 刘楠楠[4] 田菲[4] 胡运生[5] 刘锟[1] 

机构地区：[1]第四军医大学唐都医院胸腔外科,陕西西安710038 [2]第四军医大学唐都医院放疗科,陕西西安710038 [3]第四军医大学基础部电镜中心,陕西西安710033 [4]第四军医大学基础部教学实验中心,陕西西安710033 [5]第四军医大学唐都医院骨科,陕西西安710038

出　　处：《第四军医大学学报》2008年第5期461-464,共4页Journal of the Fourth Military Medical University

摘　　要：目的:探讨水飞蓟素(SM)对人肺腺癌细胞(A549)的抗癌作用及其分子机制.方法:采用倒置显微镜和电子显微镜等形态学检测、四甲基偶氮唑蓝(MTT)比色法、流式细胞仪(FCM)技术结合PI及Annexin V双标记染色以及MAPK的磷酸化活性检测方法.结果:SM对人肺腺癌A549细胞的增殖有抑制作用;SM作用A549细胞48h后,随着浓度的增加,倒置显微镜下可见细胞数目减少,有些细胞变小、变圆;透射电镜观察发现,随着SM作用浓度的增加,A549细胞中逐步出现增多的凋亡细胞,凋亡细胞表现出典型的超微结构特征;流式细胞仪检测的结果发现,随着药物作用时间的延长,A549细胞的G1期细胞比例增多,S期细胞明显减少,G2期细胞略有减少,并出现一明显的凋亡峰.SM可以抑制A549细胞中ERK的活性,并在一定程度上提高p38和JNK的活性.结论:SM可以在体外抑制人肺腺癌细胞A549的增殖作用,并诱导其凋亡.SM可能通过抑制A549细胞中ERK的活性,并提高p38和JNK的活性发挥其诱导作用.AIM： To study the anticancer effect and the molecular mechanism of silymarin on human lung adenocarcinoma cell line A549. METHODS ： The morphological characters of apoptosis induced by silymarin were studied and analyzed by inverted microscopy, electron microscopy, methyl thiazolyl tetrazolium （MTT） colorimetric assay, combination of flow cytometry （ FCM ） and Annexin V/Propidium Iodide double staining, and detection of phosphorylation activity of MAPK. RESULTS： Silymarin had a significant inhibitory effect on the proliferation of human lung adenocarcinoma cell line A549; treated with silymarin for 48 h, some of the cells became smaller and looked more round than before; The number of A549 cells showing apoptosis increased with elevation of the concentration of the silymarin, and these cells appeared typical ultrastructural features; the results of FCM indicated that the proportion of A549 cells in G1 phase increased, while the number of cells in S phase decreased significantly and those in G2 phase reduced slightly but presented a marked apoptotic peak. Silymarin had an ability of inhibiting the activity of ERK and increasing the activities of p38 and JNK to some degree in A549 cells. CONCLUSION： Silymarin can inhibit the proliferation of human lung adenocarcinoma cell line A549 in vitro and induce its apoptosis possibly through inhibiting the activity of ERK and increasing the activities of p38 and JNK in A549 cells.

关 键 词：水飞蓟素 肺肿瘤 腺癌 细胞系 凋亡 MAPK信号通路 

分 类 号：R73-33[医药卫生—肿瘤]