力达霉素联合利妥昔单抗对人B细胞淋巴瘤的治疗作用  

The synergistic effect of lidamycin and rituximab on human B cell lymphoma

作　　者：孙轶然[1] 张胜华[1] 邵荣光[1] 何红伟[1] 

机构地区：[1]中国医学科学院、北京协和医学院医药生物技术研究所,北京100050

出　　处：《药学学报》2014年第2期198-203,共6页Acta Pharmaceutica Sinica

基　　金：国家重点基础研究发展计划(973计划)资助项目(2009CB521807);国家“重大新药创制”科技重大专项(2012ZX09301-002);国家自然科学基金资助项目(81273554,81170409)

摘　　要：研究力达霉素与利妥昔单抗联合抗人B细胞淋巴瘤的作用和机制。采用MTS法检测细胞的增殖抑制率,采用Annexin V-FITC/PI法进行细胞凋亡检测,Western blotting检测细胞凋亡相关蛋白的表达量变化,最后用人B细胞淋巴瘤裸鼠模型验证该联合方案对淋巴瘤的体内抑制作用。结果表明,利妥昔单抗与力达霉素联合效果显著,增殖抑制作用和细胞凋亡比率显著多于单独用药组,信号通路分析表明凋亡相关蛋白表达升高,凋亡抑制蛋白表达下降。联合用药组荷瘤小鼠生存时间明显高于对照组和单独用药组,体内脾脏转移程度低于对照组和单独用药组。研究表明力达霉素与利妥昔单抗对人B细胞淋巴瘤的体内、体外增殖有协同抑制作用,这种联合协同机制可能与增加肿瘤细胞的凋亡有关。This study aimed to investigate the synergistic effect of lidamycin （LDM） and rituximab on human B cell lymphoma Ramos cells. Cell proliferation was measured using MTS assay, cell apoptosis was analyzed by Annexin V-FITC/PI assay, the expression of apoptosis related proteins was analyzed by Western blotting, and the in vivo lymphoma inhibition was verified using BALB/c mice inoculated via tail vein using Ramos cells which stably expressed pEGFP-N1 plasmid. The results showed that, after the pretreatment with rituximab for 48 h, rituximab and LDM showed significantly synergistic effects on cell proliferation. Cells in combined treatment group had a higher apoptosis rate than that in LDM treatment group. Compared with the LDM treatment group, the expression of apoptosis-related proteins such as Cleaved caspase-3, Cleaved caspase-7, Cleaved caspase-9 and Cleaved PARP in combined treatment groups increased, and expression of cIAP-2 and Bcl-2 decreased. The result of in vivo experiment showed that, in the combined treatment group, the survival time of BALB/c mice was significantly longer than the mice in control group and LDM treatment group, and the degree of tumor accumulation and metastasis to lymph nodes and spleen was lower.

关 键 词：力达霉素 利妥昔单抗 细胞凋亡 BCL-2 

分 类 号：R965[医药卫生—药理学]