索拉非尼诱导K562细胞凋亡机制的研究

目的：观察索拉非尼对BCR-ABL阳性细胞株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法观察索拉非尼作用48小时后K562细胞增殖活力变化；AnnexinV/PI双染法索拉非尼对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。Hochest33342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（Western blotting）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，凋亡相关蛋白PARP剪切。结论：PARP剪切为执行凋亡功能的casepase途径活化的一个标记，提示索拉非尼诱导K562细胞凋亡的机制同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CML及伊马替尼耐药的CML具有潜在的应用前景。

Mechanism of sorafenib in inducing apoptosis of K562 cells

To observe the effect of Sorafenib on BCR/ABL positive cell K562 proliferation, apoptosis and investigate the exact mechanism. METHODS: K562 cell was treated with different concentration of Sorafenib for 48h. Cell viability rate was determined by CCK-8 assay. Apoptosis analysis was conducted by AnnexinV/PI、PI staining and Hochest 33342. PARP protein was detected by Western blotting. RESULT: Sorafenib induces K562 cell growth inhibitory and apoptosis in dose-dependent manner with PARP protein cleaved. CONCLUSIONS: PARP cleavage as a measure of activation of caspase cascades. The inducing apoptosis effect of Sorafenib on K562 cell may have relation with activation of caspase casecades. Sorafenib may be an effective therapeutic measure to treat imatinib-resistant CML.