藤黄酸对弥漫性大B淋巴瘤细胞株OCI-LY-1增殖和凋亡的影响及其分子学机制  

Effect of gambogic acid on proliferation and apoptosis of human diffuse large B-cell lymphoma cell line OCI-LY-1

作　　者：师宪平[1] 蓝晓莹[1] 陈鑫[1] 王文文[2] 温创宇[3,4] 黄美近[4] 刘焕亮[3,4] 

机构地区：[1]广州医学院免疫研究所,广东广州510182 [2]中山大学附属第三医院血液内科,广东广州510630 [3]中山大学胃肠病学研究所,广东广州510655 [4]中山大学附属第六医院,广东广州510655

出　　处：《中国病理生理杂志》2013年第5期815-820,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81100378);广州市科信局应用基础研究专项重点项目(No.2012J4100014);广东省医学科研基金(No.B2012159)

摘　　要：目的:探讨藤黄酸对弥漫性大B淋巴瘤细胞增殖与凋亡的影响及其分子学机制,研究藤黄酸治疗弥漫性大B细胞淋巴瘤的潜在应用价值。方法:用藤黄酸处理细胞,采用MTS法对淋巴瘤细胞进行细胞活力及增殖抑制测定;碘化丙啶(PI)单染荧光显微镜观察细胞形态改变;采用AnnexinⅤ-FTIC/PI流式细胞术检测细胞凋亡;利用Western blotting检测蛋白酶体系统相关蛋白(Ubs、Bax、HSP90和IκB-α)、凋亡相关蛋白(PARP、pro-caspase-3和caspase-8)及细胞增殖信号通路相关蛋白(ERK和STAT5)的变化情况。结果:藤黄酸明显抑制OCI-LY-1细胞的增殖活性,诱导OCI-LY-1细胞呈凋亡趋势;随藤黄酸浓度升高,Ubs、Bax和HSP90表达升高;随藤黄酸浓度升高与作用时间延长,PARP切割、pro-caspase-3、pro-caspase-8、ERK、p-ERK、STAT5及p-STAT5表达下降。结论:藤黄酸抑制弥漫性大B淋巴瘤细胞株的蛋白酶体活性,抑制细胞增殖,促进细胞凋亡。AIM ： To investigate the effects of gambogic acid （GA） on the proliferation and apoptosis of human diffuse large B-cell lymphoma cells. METHODS： Diffuse large B-cell lymphoma cell line OCI-LY-19 was treated with GA. The cell viability and proliferation were evaluated by MTS assay. The morphological changes of the cells were observed under inverted microscope and fluorescence microscope with PI staining. The cell apoptosis was detected by flow cytometry. The changes of proteasome-related proteins Ubs, Bax, HSP90 and IκB-a, the apoptosis-related proteins PARP, pro- caspase-3 and caspase-8, and the proliferation-associated molecules ERK and STATS were detected by Western blotting. RESULTS： The proliferation of OCI-LY-19 cells was inhibited and the apoptosis was induced by GA. The expression of Ubs, Bax and HSP90 was up-regulated by GA treatment in a dose-dependent manner. The PARP protein was cleaved. The levels of apoptosis-related proteins pro-caspase-3 and pro-caspase-8, and proliferation-associated molecules p-Akt, p-ERK and p-STATS were down-regulated by GA treatment in a dose- and time-dependent manner. CONCLUSION： Gambogic acid down-regulates the activity of proteasome, inhibits cell proliferation and promotes cell apoptosis of diffuse large B cell lymphoma.

关 键 词：弥漫性大B淋巴瘤 藤黄酸 蛋白酶体 细胞增殖 细胞凋亡 

分 类 号：R733.4[医药卫生—肿瘤]