Zhang Bao-Zhen, Ren Han-Yun
Department of Hematology, Peking University First Hospital, Beijing 100034, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2007 Dec;15(6):1182-5.
This study was aimed to investigate the effect of STI571, an inhibitor of tyrosine kinase, on the proliferation and apoptosis of chronic myelogenous leukemia (CML) cells as well as expression of anti-apoptotic protein Mcl-1, and to explore the possible role of Mcl-1 in apoptosis-inducing mechanism. K562 cell line was used to observe the effect of STI571 on CML cells. Proliferation and cytotoxicity were analyzed by MTT assay. The apoptotic cells were labelled with Annexin V-FITC and PI and then analyzed by flow cytometry. The expression of apoptotic-related proteins in K562 cells was determined by Western blot with specific antibodies. The results showed that STI571 significantly inhibited the proliferation and induced apoptosis of K562 cells in a dose-and time-dependent manner. Coincidently, the protein phosphorylation on tyrosine residues was reduced and the expressions of anti-apoptotic protein Mcl-1 and Bcl-xl were down-regulated after exposure to STI571. It is concluded that STI571 induces the apoptosis of CML cells by down-regulating the expressions of Mcl-1 and Bcl-xl, which suggests that Mcl-1 and Bcl-xl may play an important role in anti-apoptotic process of CML cells.
本研究旨在探讨酪氨酸激酶抑制剂STI571对慢性粒细胞白血病（CML）细胞增殖、凋亡以及抗凋亡蛋白Mcl-1表达的影响，并探讨Mcl-1在凋亡诱导机制中的可能作用。采用K562细胞系观察STI571对CML细胞的作用。通过MTT法分析细胞增殖和细胞毒性。用Annexin V-FITC和PI标记凋亡细胞，然后通过流式细胞术进行分析。用特异性抗体通过蛋白质免疫印迹法检测K562细胞中凋亡相关蛋白的表达。结果显示，STI571以剂量和时间依赖性方式显著抑制K562细胞的增殖并诱导其凋亡。同时，暴露于STI571后，酪氨酸残基上的蛋白质磷酸化减少，抗凋亡蛋白Mcl-1和Bcl-xl的表达下调。结论是，STI571通过下调Mcl-1和Bcl-xl的表达诱导CML细胞凋亡，这表明Mcl-1和Bcl-xl可能在CML细胞的抗凋亡过程中发挥重要作用。
