TWS119对多发性骨髓瘤细胞增殖及凋亡影响机制研究  

Effects study of TWS119 on the proliferation and apoptosis of multiple myeloma cells

作　　者：李彦辰 邹露 熊福龙 戴世溧 张昊[1] 周亮[1] LI Yanchen;ZOU Lu;XIONG Fulong;DAI Shili;ZHANG Hao;ZHOU Liang(Department of Pharmacology,College of Pharmaceutical Sciences,Soochow University,Suzhou,Jiangsu 215123,China)

机构地区：[1]苏州大学药学院药理系,江苏苏州215123

出　　处：《现代医药卫生》2022年第6期901-905,911,共6页Journal of Modern Medicine & Health

基　　金：国家自然科学基金项目(32170975);苏州大学江苏省高等学校大学生创新创业训练计划项目(202010285065)。

摘　　要：目的研究糖原合成酶激酶-3β(GSK-3β)抑制剂TWS119对多发性骨髓瘤(MM)细胞凋亡和增殖的影响。方法使用TWS119处理MM细胞系LP1和MM1.S,收集细胞进行免疫印迹实验和细胞增殖实验,运用caspase抑制剂z-VAD-fmk或Calpain抑制剂Calpeptin处理,研究TWS119对LP1和MM1.S凋亡和增殖的影响。最后,联合TWS119和蛋白酶体抑制剂硼替佐米(Btz)处理MM细胞,观察MM细胞Btz敏感性。结果LP1和MM1.S细胞中,TWS119能够显著促进细胞凋亡,抑制细胞增殖。抑制caspase或Calpain信号通路不能削弱TWS119在MM细胞中的毒性。TWS119可显著增加MM细胞Btz敏感性。结论TWS119能够通过caspase非依赖方式来促进MM细胞凋亡,抑制MM细胞增殖,并且增加MM细胞Btz敏感性。Objective To study the effect of TWS119,a glycogen synthase kinase-3β(GSK-3β)inhibitor,on the apoptosis and proliferation of multiple myeloma(MM)cells.Methods The MM cell lines LP1 and MM1.S were treated with TWS119,and the cells were collected for Western blotting and cell proliferation experiments,which was treatmented with caspase inhibitor z-VAD-fmk or Calpain inhibitor Calpeptin to study the effect of TWS119 on the apoptosis and proliferation of LP1 and MM1.S.Finally,MM cells were treated with TWS119 and bortezomib(Btz,a proteasome inhibitor),the Btz sensitivity of MM cells was observed.Results TWS119 could significantly promote apoptosis and inhibit cell proliferation in LP1 and MM1.S cells.Subsequent inhibition of caspase or Calpain signaling pathway could not weaken the toxicity of TWS119 in MM cells.TWS119 could significantly increase the Btz sensitivity of MM cells.Conclusion TWS119 can promote the apoptosis of MM cells,inhibit the proliferation of MM cells,and increase the Btz sensitivity of MM cells in a caspase-independent manner.

关 键 词：多发性骨髓瘤 凋亡 增殖 TWS119 CASPASE 信号通路 

分 类 号：R733.1[医药卫生—肿瘤] R966[医药卫生—临床医学]