U0126增强索拉非尼对K562细胞增殖抑制、凋亡及诱导分化作用

目的: 观察索拉非尼、索拉非尼联合MEK激酶抑制剂U0126对人慢性粒细胞白血病K562细胞株增殖、凋亡及分化的影响,并初步探讨其机制。方法: CCK-8法观察索拉非尼、U0126单用及不同浓度索拉非尼联合10 μmol/L U0126作用K562细胞48 h后细胞增殖活力变化;PI单染法及Hoechst 33342染色法观察索拉非尼、U0126单用及索拉非尼联合U0126对K562细胞株的凋亡诱导作用;细胞周期分析及联苯胺染色观察索拉非尼、U0126单用及低浓度索拉非尼联合U0126是否诱导K562细胞株向红系分化;采用免疫印迹法检测c-Myc蛋白表达。结果: MEK抑制剂U0126增强了索拉非尼对K562细胞增殖抑制、促凋亡及诱导分化作用。两药联用显著下调K562细胞c-Myc蛋白水平。结论: MEK抑制剂U0126增强索拉非尼对K562细胞增殖抑制、凋亡及诱导分化作用,这可能与其协同下调c-Myc蛋白有关。

U0126 enhances sorafenib-induced proliferation inhibition, apoptosis and differentiation in K562 cells

AIM: To observe the effects of sorafenib and sorafenib combined with an MEK kinase inhibitor U0126 on the proliferation, apoptosis and differentiation in human chronic myelogenous leukemia cell line K562. METHODS: K562 cells were treated with different concentrations of sorafenib and U0126 or 10 μmol/L U0126 combined with different concentrations of sorafenib for 48 h. Cell inhibitory rate was determined by CCK-8 assay. Apoptosis analysis was conducted by Hoechst 33342 and PI staining. Cell cycle analysis and benzidine staining were used to confirm K562 cells towards erythroid differentiation. The protein expression of c-Myc was detected by Western blotting. RESULTS: U0126 enhanced sorafenib-induced proliferation inhibition, apoptosis and differentiation in K562 cells. Sorafenib combined with U0126 remarkably reduced the protein level of c-Myc. CONCLUSION: U0126 synergistically enhances sorafenib-induced proliferation inhibition, apoptosis and differentiation in K562 cells through reducing c-Myc protein level.