摘要
目的观察索拉非尼对BCR-ABL阳性人慢性粒细胞白血病细胞株K562的增殖、凋亡作用,探索多靶点抗肿瘤药物索拉非尼诱导K562细胞凋亡可能机制。方法 CCK-8法观察索拉非尼0、5、7.5、10、12.5、15、20μmol/L作用48 h后K562细胞增殖活力变化;AnnexinV/PI双染法观察索拉非尼0、5、10、15、20μmol/L对K562细胞株的早期凋亡诱导作用;PI单染法观察索拉非尼对K562细胞株晚期凋亡诱导作用。Hochest 33342染色法观察索拉非尼所致K562细胞凋亡形态学变化。免疫印迹法检测凋亡相关蛋白PARP变化。结果索拉非尼以浓度依赖的方式抑制K562细胞株增殖,诱导细胞凋亡及凋亡相关蛋白PARP剪切。结论 PARP剪切是执行凋亡功能的caspase途径活化的一个标记,提示索拉非尼诱导K562细胞凋亡的机制与caspase级联反应活化有关,多靶点抗肿瘤药物索拉非尼用于治疗慢性粒细胞白血病及伊马替尼耐药的慢性粒细胞白血病具有潜在的应用前景。
Objective To observe the effects of sorafenib on proliferation and apoptosis of BCR/ABL positive human chronic myelogenous leukemia cell -line K562. Methods K562 cells were cultured with different concentrations of sorafenib （0, 5, 7.5, 10, 12.5, 15 and 20 μmoL/L） for 48 h. Cell viability was determined by CCK- 8 assay. Apoptosis was conducted by AnnexinV/PI, PI staining and Hochest 33342. PARP protein was detected by Western blotting. Results Sorafenib induced inhibition of cell growth, cell apoptosis and PARP cleavage were observed in dose - dependent manners. Conclusion PARP cleavage, a marker of caspase cascades activation, is induced by sorafenib, suggesting that sorafenib induces K562 apoptosis via this pathway. Thus it provides therapeutic effects of sorafenib on imatinib - resistant chronic myeloid leukemia.
出处
《广东医学》
CAS
CSCD
北大核心
2011年第11期1402-1405,共4页
Guangdong Medical Journal
基金
广东省科技计划项目(编号:2006B35501008)
