硼替佐米通过内质网应激途径增强力达霉素对人多发性骨髓瘤细胞SKO-007凋亡诱导作用  

Apoptosis-induction of lidamycin in human multiple myeloma SKO-007 cells enhanced by bortezomid through endoplasmic reticulum stress pathway

作　　者：甄永占[1] 纪春梅[2] 赵毓芳[1] 闫丰[3] 刘学军[3] 王梅梅[1] 徐爱军[1] 

机构地区：[1]河北联合大学基础医学院组织学与胚胎学教研室,河北唐山063000 [2]河北省唐山市协和医院呼吸内科,河北唐山063000 [3]河北联合大学附属医院肿瘤科,河北唐山063000

出　　处：《吉林大学学报（医学版）》2013年第6期1206-1210,1315,共6页Journal of Jilin University：Medicine Edition

基　　金：河北省科技厅自然科学基金资助课题(H2012401030)

摘　　要：目的:研究力达霉素(LDM)联合硼替佐米(BZM)的抗骨髓瘤作用,并探讨两药联合协同抗骨髓瘤的作用机制。方法:选取处于对数生长期人多发性骨髓瘤细胞SKO-007随机分为对照组、LDM组、BZM组和LDM+BZM联合组,采用MTS法和流式细胞术检测各组细胞存活率、细胞周期分布和凋亡率;采用Western blotting法检测各组SKO-007细胞凋亡相关蛋白和内质网应激(ERS)相关蛋白的表达量。结果:细胞培养48h后,LDM+BZM联合组细胞存活率显著低于LDM组、BZM组和对照组(P<0.05);LDM+BZM联合组SKO-007细胞G2/M期的细胞比例、细胞凋亡率、caspase-3和poly ADP-ribose polymerase(PARP)的切割片段蛋白表达量、GRP78/Bip蛋白表达量、CHOP/GADDl53蛋白表达量和c-Jun氨基末端激酶(JNK)蛋白磷酸化(p-JNK)表达量明显高于LDM组、BZM组和对照组(P<0.05)。结论:BZM通过上调caspase-3和PARP的切割片段蛋白表达量,进一步激活ERS介导的凋亡途径,增强LDM的抗骨髓瘤作用。Objective To investigate the effect of lidamycin （LDM） combined with bortezomid （BZM） against multiple myeloma and the mechanism of the combination treatment. Methods The human multiple myeloma SKO-007 cells in logarithm growth phase were selected and randomly divided into control group, LDM group, BZM group, and BZM combined with LDM group. MTS assay was used to detect the survival rate of SKO-007 cells and flow cytometry was used to analyze the distribution of cell cycle and apoptotic rate of the proliferation cells in various groups; the expression levels of protein associated with apoptosis and endoplasmic reticulum stress （ERS） of SKO-007 cells in various groups were detected by Western blotting method. Results After culture for 48 h, the survival rate of the cells in BZM combined with LDM group was lower than those in control, LDM and BZM groups （P〈0.05）. The percentage of cells at G2/M phase, the apoptotic rate of cells, the expression levels of cleaved caspase-3 and poly ADP-ribose polymerase （PARP） of SKO-007 cells, the expression levels of GRP78/Bip, CHOP/GADD153, and phosphorylation of c-Jun NH2-terminal kinase （p-JNK） in BZM combined with LDM group were higher than those in control, LDM and BZM groups （all P〈0.05）. Conclusion BZM can greatly enhance the efficacy of LDM against multiple myeloma by increasing the levels of cleaved caspase-3 and PARP, and remarkably increase the apoptosis induced by LDM through further activation of ERS.

关 键 词：硼替佐米 力达霉素 多发性骨髓瘤 联合用药 内质网应激 

分 类 号：R73[医药卫生—肿瘤]