雷公藤内酯醇对弥漫性大B淋巴瘤细胞株凋亡的影响及其机制探讨  

Effect and mechanism of triptolide on the apoptosis of human diffuse large B-cell lymphoma cell line OCI-LY-19

作　　者：师宪平[1] 蓝晓莹[1] 温创宇[2,3] 陈鑫[1] 刘焕亮[2,3] 

机构地区：[1]广州医学院免疫研究所,广州510182 [2]中山大学胃肠病学研究所 [3]中山大学附属第六医院

出　　处：《山东医药》2013年第6期1-3,共3页Shandong Medical Journal

基　　金：国家自然科学基金资助项目(81100378);广州市科信局应用基础研究专项重点项目(2012J4100014);广东省医学科研基金(B2012159)

摘　　要：目的探讨雷公藤内酯醇(TPL)对弥漫性大B淋巴瘤细胞株SU-DHL-4凋亡的影响及作用机制,为其临床应用提供依据。方法分别采用0、0.031 25、0.062 5、0.125、0.25及0.5μmol/L(μM)的TPL作用于SU-DHL-4细胞,采用MTS法测定细胞增殖活性;分别采用0、0.1、0.2、0.3μM的TPL作用于SU-DHL-4细胞,采用AnnexinV/PI双染流式细胞术测定细胞凋亡率,Western blot法检测细胞凋亡相关蛋白(PARP、Pro-caspase3、Pro-caspase8、XI-AP、Mcl-1)及细胞增殖相关蛋白(AKT、ERK、STAT5)表达。结果 0.125μM以上的TPL能明显抑制SU-DHL-4细胞的增殖活性,细胞半数致死量所需药物浓度为0.131μM;随TPL浓度升高与作用时间延长,凋亡细胞数逐渐增多;PARP活化,Pro-caspase3、Pro-caspase8、XIAP、Mcl-1表达下降,AKT、ERK、STAT5及其磷酸化形式P-AKT、P-ERK、P-STAT5的表达下降。结论 TPL能抑制弥漫性大B淋巴瘤细胞株SU-DHL-4生长,诱导其凋亡。其机制可能为抑制细胞凋亡蛋白表达、抑制增殖相关蛋白表达及激活Caspase级联反应。Objective To investigate the effects of triptolide on the induction of apoptosis of human diffuse large B- cell lymphoma SU-DHL-4 cells. Methods SU-DHL-4 cells were treated with different concentrations of triptolide. Cellu- lar proliferation was measured with MTS assay. Cell apoptosis was analyzed by flow cytometry with AnnexinV/PI staining. The expression of apoptosis-relative and proliferation-relative proteins were analyzed by Western blot. Results The prolif- eration of SU-DHL-4 cell was inhibited as the concentrations of triptolide reach 0. 125 Ixmol/L and the ICs0 is 0. 131 txmol/ L. The percentage of apoptotic ceU was increased in a triptolide time and concentration dependent manner. The PARP pro- teins were cleaved. The expressions of apoptosis-related proteins Pro-caspase3, Pro-caspase8, XIAP, Mcl-1 and prolifera- tion-relative proteins P-AKT, P-ERK and P-STATS were down-regulated in a triptolide dose and time dependent manner. Conclusion Triptolide can induce apoptosis of SU-DHL-4 cells and the mechanism may associate with cleave and down- regulation of apoptosis-related proteins and proliferation-related proteins.

关 键 词：雷公藤内酯醇 弥漫性大B淋巴瘤 细胞凋亡 

分 类 号：R733.4[医药卫生—肿瘤]