藤黄酸诱导Burkitt淋巴瘤细胞株凋亡及增殖抑制的分子学机制  

Molecular Mechanism of Apoptosis and Proliferation Inhibition Induced by Gambogic Acid in Burkitt Lymphoma Cell Line

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

机构地区：[1]广州医科大学免疫研究所,广东广州510182 [2]广州医科大学生化教研室,广东广州510182 [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：《中山大学学报（医学科学版）》2013年第4期526-530,共5页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金(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】研究藤黄酸对Burkitt淋巴瘤细胞株Namalva细胞增殖与凋亡的影响及其分子学机制,探讨藤黄酸治疗Burkitt淋巴瘤的潜在应用价值。【方法】用不同剂量藤黄酸处理细胞,采用MTS法对淋巴瘤细胞进行细胞活力及增殖抑制测定;0.25、0.5、0.75μmol/L藤黄酸分别处理细胞24 h,0.75μmol/L藤黄酸分别处理细胞6、12、24h后收集细胞,采用AnnexinⅤ-FTIC/PI流式细胞术检测藤黄酸剂量依赖性细胞凋亡情况;利用Western blot方法检测凋亡相关蛋白和细胞增殖信号通路相关蛋白剂量与时间依赖的变化情况。【结果】藤黄酸明显抑制Namalva细胞的增殖,诱导Namalva细胞发生凋亡。随藤黄酸浓度升高与作用时间延长,细胞中PARP,caspase 8出现切割,Bax表达上调,Pro-caspase 3,Pro-caspase 9,Bcl-2表达下调。增殖通路蛋白STAT5、p-STAT5、ERK、p-ERK的表达受到明显抑制。【结论】藤黄酸通过影响Burkitt淋巴瘤细胞株Namalva细胞凋亡相关蛋白的表达,促进细胞凋亡;通过抑制JAKs/STATs、MEK/ERK信号转导通路的活化,抑制Burkitt淋巴瘤细胞的增殖。[ Objective ] To study the influence of gambogic acid on the proliferation and cell apoptosis of Burkitt lymphoma cells Namalva, and provide basis for clinical treatment of Burkitt lymphoma. [ Methods ] Burkitt lymphoma cells were treated with different doses of gambogic acid. The cell viability and proliferation were evaluated by MTS assay. Cells were treated with 0.25, 0.5, and 0.75 μmol/L gambogic acid for 24 hours, and 0.75 μmol/L gambogic acid for respectively 6, 12, and 24 h. The dose-dependent cell apoptosis was detected using flow cytometry with Annexin V-FTIC/PI staining. The dose- and time-dependent changes of apoptosis and proliferation-related proteins were tested by Western blotting. [Results] The cell viability was inhibited by gambogic acid. Gambogic acid induced Namalva cell apoptosis and the cleavage of PARP and caspase 8, upregulated Bax, and decreased the expression of Pro-caspase 3, Pro-caspase 9, and Bcl-2 as well as proliferation pathway and related protein STAT5, p-STATS, ERK, p-ERK in a dose and time dependent manner. [Conclusion] Gambogic acid induces cell apoptosis by effecting the expression of apoptosis related proteins and inhibits cell proliferation by down-regulating the activation of JAKs/STATs, MEK/ERK signal transduction pathway in Burkitt lymphoma cells.

关 键 词：BURKITT淋巴瘤 藤黄酸 细胞增殖 细胞凋亡 

分 类 号：R733.4[医药卫生—肿瘤]