新型蒽醌类衍生物HG251诱导人白血病K562/DOX细胞凋亡的机制

Antitumor mechanism of HG251,a novel anthracene derivative,in K562/DOX leukemia cells

目的探讨新型蒽醌类衍生物HG251诱导K562/DOX细胞凋亡的机制。方法以MTT法检测细胞活力,流式细胞仪检测细胞周期变化、凋亡率、线粒体膜电位的变化,Western blot检测P-gp及凋亡相关蛋白如半胱天冬蛋白酶-3、-8、-9、p53、Bcl-xL、cytochrome C的表达。结果HG251剂量依赖性的抑制K562/DOX细胞的生长、降低线粒体膜电位并诱导其凋亡;上调p53并下调Bcl-xL;诱导半胱天冬蛋白酶-3、-8、-9的活化及cytochrome C的释放,但对P-gp的表达无影响。结论HG251通过干扰p53及Bcl-xL的表达而克服K562/DOX细胞的多药耐药,并通过细胞膜死亡受体途径及线粒体途径诱导其细胞凋亡。

Aim To evaluate the mechanism of HG251-induced apoptosis in K562/DOX cells. Methods Cell viability was assessed by MTT assay;cell cycle distribution,apoptosis and mitochondrial membrane potential were measured by flow cytometry;the protein expressions of P-gp, caspase-3, caspase-8, caspase-9, p53,Bcl-xL and cytochrome c in the K562/DOX cells were evaluated by Western blot. Results HG251 was able to inhibit cells proliferation,induce apoptosis,lose mitoehondrial membrane potential, activate caspase-3,caspase-8, caspase-9, up-regulate p53 protein and down-regulate Bel-xL protein in a dose-dependent manner but it had no effect on P-gp protein expression. Conclusion HG251 could overcome apoptotic resistanee via up-regulating p53 protein and down-regulating Bcl-xL protein. In addition, HG251 also induced K562/ DOX cells apoptosis via mitochondrial pathway and membrane death receptor pathway.