硼替佐米对老年白血病患者原代细胞增殖、凋亡及其bcl-2家族蛋白表达的影响

Effect of bortezomib on proliferation, apoptosis and expression of bcl-2 family proteins in primary acute leukemia cells from elderly patients

目的 研究硼替佐米对老年白血病原代细胞增殖、凋亡及其bcl-2家族蛋白表达的影响。方法 MTT比色法检测细胞增殖活力；荧光显微镜形态观察、流式细胞仪检测细胞凋亡；Western-blot检测Bcl-2、Bax蛋白表达。结果 50～5000nM硼替佐米均可抑制细胞增殖并诱导凋亡，其中50nM和5000nM处理细胞24h，细胞增殖活力分别下降至90%和70%，细胞凋亡率分别为10.2±2.3%和13.3±3.3%；延长处理时间至48h，细胞活力进一步下降至86%和60%，细胞凋亡率增至18.4±3.9%和20.7±3.7%，与对照组相比差异均具有统计学意义（P值均〈0.05）；50～5000nM硼替佐米处理细胞24-48h，Bcl-2蛋白表达逐渐下降，Bax蛋白表达逐渐增加。结论 硼替佐米对老年白血病原代细胞具有抑制增殖、诱导凋亡作用，其作用机制可能与Bcl-2家族蛋白的表达水平变化相关。

Abstract： Objective To research the antitumous effect and mechanism of bortezomib on primary acute leukemia cells from elderly patients. Methods Primary acute leukemia cells were treated with bortezomib 50-5000nM for 24h-48h,Cell proliferation was analysed by MTT assay;the apoptosis of primary acute leukemia cells was observed by fluorescence microscope and flow cytometry;protein expression of Bcl-2 and Bax was detected by western-blot. Result： The cell viability was 90% and 70% when leukemia cells treated by 50nM and 5000nM bortezomib for 24h,respectively.meanwhile,the apoptosis rate of these concentrations was 10.2±2.3% and 13.3±3.3%. Prolonged the time for 48h,the cell viability decreased to 86% and 60%,respectively.And in the same condition,the apoptosis rate was increased to 18.4±3.9% and 20.7±3.7%;Compared with the control group, the differences were statistically significant,P value 〈0.05.With the increase of bortezomib concentration,the Bcl-2 protein expression was decreased,while Bax protein expression was increased. Conclusion： Bortezomib can inhibit primary leukemia cell proliferation and induce apoptosis.The mechanism is associated with the expressive change of bcl-2 family protein.