Bortezomib增强三氧化二砷抑制KM3细胞生长和促凋亡机制的研究  

Arsenic trioxide inhibits KM3 cell growth and induces apoptosis and potentiated by bortezomib

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

出　　处：《中国病理生理杂志》2010年第2期297-301,共5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:新的治疗药物及方法的出现大大提高了多发性骨髓瘤(MM)的疗效,但仍然无法使其治愈。为了寻求治疗药物及方法,提高单药或联合用药对MM的治疗效果。我们观察了三氧化二砷(ATO,As2O3)单药及联合硼替佐米(Velcade,PS-341)有无增强诱导MM细胞凋亡的作用,并初步探讨其机制。方法:检测ATO单药及联合硼替佐米对KM3细胞的影响。应用台盼蓝拒染法检测细胞活力,MTT(四甲基偶氮唑盐比色法)检测细胞生长抑制率。流式细胞术检测细胞的凋亡比例。应用RT-PCR方法检测p65mRNA的表达变化。应用Western blotting检测p65、p-p65、PARP、caspase-3、-8、-9蛋白表达的变化。结果:ATO抑制细胞生长,对KM3细胞p65mRNA及其蛋白没有显著影响,主要是通过激活caspase-3,-8,-9,诱导细胞凋亡。当与bortezomib联合用药时有协同促凋亡作用。结论:ATO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 observe if there is a synergistical effect on induction of apoptosis when arsenic trioxide alone or combination with bortezomib in KM3 cells. METHODS ： KM3 cells were treated with arsenic trioxide alone or combined with bortezomib, the numbers of viable cells were determined by trypan blue exclusion. Cell growth inhibition was examined by MTT method. The cells were simultaneously stained with annexin V - FITC and PI and apoptosis was determined by bivariate flow cytometry using a FACScan. Reverse trascriptional - PCR （ RT - PCR） method was used to examine the change of p65 mRNA and Western blotting to measure the expression of protein p65, p - p65, caspase - 3, - 8, - 9, and poly ADP- ribose polymerase （PARP）. RESULTS： Arsenic trioxide inhibited the cell growth and induced apoptosis. The mechanism was responsible for the activation of caspase - mediated induction of apoptosis. A synergistic effect of combination with bortezomib on apoptosis was observed. CONCLUSION： Arsenic trioxide inhibits KM3 cell growth and induces apoptosis with a synergistical effect when cotreated with bortezomib.

关 键 词：三氧化二砷 硼替佐米 细胞凋亡 多发性骨髓瘤 KM3细胞 

分 类 号：R733.3[医药卫生—肿瘤]