CAJ | 학술논문

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,As_2O_3)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.
목적:신적치료약물급방법적출현대대제고료다발성골수류(MM)적료효,단잉연무법사기치유.위료심구치료약물급방법,제고단약혹연합용약대MM적치료효과.아문관찰료삼양화이신(ATO,As_2O_3)단약급연합붕체좌미(Velcade,PS-341)유무증강유도MM세포조망적작용,병초보탐토기궤제.방법:검측ATO단약급연합붕체좌미대KM3세포적영향.응용태반람거염법검측세포활력,MTT (사갑기우담서염비색법)검측세포생장억제솔.류식세포술검측세포적조망비례.응용RT-PCR방법검측p65mRNA적표체변화.응용Western blotting검측p65、p-p65、PARP、caspase-3、 -8、-9단백표체적변화.결과:ATO억제세포생장,대KM3세포p65mRNA급기단백몰유현저영향,주요시통과격활caspase-3,-8,-9,유도세포조망.당여bortezomib연합용약시유협동촉조망작용.결론:ATO단독작용우KM3세포가이억제기생장병유도세포조망,여bortezomib련용시유협동효응.
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.