DADS通过MAPK和PI3K/Akt信号通路下调Mcl-1诱导白血病细胞凋亡  

Diallyl Disulfide Downregulates Mcl-1 via the MAPK and PI3K/Akt Pathway during the Apoptosis of Leukemia Cells

作　　者：谭晖[1] 吉晓霞[1] 易岚[1] 夏红[1] 王娟[1] 何洁[1] 凌晖[1] 苏琦[1] 

机构地区：[1]南华大学肿瘤研究所,湖南省衡阳市421001

出　　处：《中国肿瘤临床》2011年第12期691-695,共5页Chinese Journal of Clinical Oncology

基　　金：湖南省自然科学基金(编号:07JJ6155);湖南省普通高等学校(南华大学)重点实验室资助~~

摘　　要：目的:二烯丙基二硫(DADS)为天然植物大蒜中的提取物,能抑制多种肿瘤细胞生长,本文探讨丝裂原激活的蛋白激酶(MAPKs)、3-磷酸肌醇激酶(PI3K/Akt)信号通路和Bcl-2家族成员在DADS诱导的人白血病HL-60细胞凋亡中的作用。方法:利用流式细胞术检测DADS诱导的白血病细胞凋亡,Western blot研究MAPKs和PI3K/Akt信号通路在DADS诱导的人白血病HL-60细胞凋亡中的变化及对Bcl-2家族凋亡相关蛋白表达的影响。结果:DADS呈浓度和时间依赖性地诱导人白血病HL-60细胞凋亡,在此过程中ERK/MAPK和PI3K/Akt信号通路被抑制,而p38MAPK信号通路被激活,ERK/MAPK和PI3K/Akt信号通路通过降低Mcl-1(myeloid cell leukemia-1)和升高Bax的表达诱导人白血病细胞凋亡,而p38MAPK则不是通过调控Mcl-1和Bax的表达诱导人白血病细胞凋亡,进一步利用RNA干扰技术沉默Mcl-1基因可增加DADS对HL-60细胞增殖抑制和诱导凋亡作用。结论:MAPK和PI3K/Akt信号通路通过下调Mcl-1的表达参与了DADS诱导的HL-60细胞凋亡作用。Objective： To investigate the role of MAPKs, phosphatidylinositol 3-kinase-Akt pathway, and the Bcl-2 family proteins in diallyl disulfide （DADS）-induced apoptosis. Methods： Flow cytometry analysis was used to detect apoptotic cells. Western blot analysis of the expression of phospho-MAPKs （ ERK and p38 ）, phospho-AKT, and the Bcl-2 family proteins was used to elucidate the possible mechanisms of DADS-induced apoptosis. Results： DADS induced significant apoptosis, which exhibited a dose-dependent and time-dependent response （ P 〈 0.05 ）. DADS inhibited the ERK/MAPK and the PI3K/AKT pathways, followed by the downregula- tion of the anti-apoptotic factor Mcl-1 and the upregulation of the pro-apoptotic factor Bax. The P38/MAPK pathways were activated and did not affect the expression of Mcl-1 and Bax. Small interfering RNA-mediated downregulation of Mcl-1 significantly sensitized the leukemia cells to DADS-induced apoptosis. Conclusion： These results clearly demonstrate that the PI3K/AKT and MAPK signaling path-way is involved in the induction of apoptosis by DADS and it is mediated by the downregulation of Mcl-1 in human HL-60 cells.

关 键 词：二烯丙基二硫HL-60细胞凋亡信号转导Mcl-1 

分 类 号：R733.7[医药卫生—肿瘤] R285.5[医药卫生—临床医学]