雷利度胺单独及联合硼替佐米抑制KM3细胞生长、诱导凋亡的机制研究  

Lenalidomide alone or combined with bortezomib inhibits growth and induces apoptosis in KM3 cells

作　　者：王清[1,2] 李娟[1] 谷景立[1] 刘俊茹[1] 曾丽金[1] 

机构地区：[1]中山大学附属第一医院血液科,广东广州510080 [2]贵州省人民医院血液科,贵州贵阳550001

出　　处：《中国病理生理杂志》2011年第7期1302-1308,共7页Chinese Journal of Pathophysiology

基　　金：广东省自然科学基金资助项目(No.8151008901000064)

摘　　要：目的:观察雷利度胺(lenalidomide)单药及联合硼替佐米(bortezomib)诱导多发性骨髓瘤(MM)KM3细胞凋亡的作用,并初步探讨其机制。方法:应用台盼蓝拒染法检测单药雷利度胺及与bortezomib联合对KM3细胞生长抑制的影响;应用流式细胞术检测细胞凋亡;应用RT-PCR方法检测p65 mRNA的表达情况;应用Western blotting检测P65(protein 65)、pP65(phosphorylated p65)、PARP[poly ADP(ribose)polymerase]及caspase-3、-8、-9蛋白的表达变化。结果:雷利度胺可以抑制KM3细胞生长,抑制p65 mRNA及其蛋白的表达,并激活caspase-8、-3及PARP,诱导细胞凋亡。雷利度胺与bortezomib联合时有协同促细胞凋亡作用。结论:雷利度胺单独作用于KM3细胞可以抑制其生长并诱导细胞凋亡,与bortezomib联用时有协同效应。AIM： To investigate the effects of lenalidomide alone or combined with bortezomib on induction of apoptosis in multiple myeloma（MM） KM3 cells.METHODS： The KM3 cells were treated with lenalidomide alone or combined with bortezomib.The number of viable cells was determined by trypan blue exclusion.Apoptotic cells were simultaneously stained with annexin V-FITC and PI and determined by flow cytometry.RT-PCR was used to examine the level of p65 mRNA.Western blotting was used to examine the protein levels of P65,pP65,caspase-3,-8,-9,and poly（ADP-ribose） polymerase（PARP）.RESULTS： Lenalidomide-inhibited the cell growth and induced apoptosis of KM3 cells.The mechanism responsible for lenalidomide-mediated inhibition was via NF-κB and activation of caspase-mediated induction of apoptosis.A synergistic effect was observed when combination of lenalidomide with bortezomib was used.CONCLUSION： Lenalidomide inhibits the growth and induces apoptosis in KM3 cells.There is a synergistical effect when combination of lenalidomide with bortezomib is in use.

关 键 词：雷利度胺 硼替佐米 细胞凋亡 多发性骨髓瘤 

分 类 号：R733.3[医药卫生—肿瘤]