AG490抑制K562细胞增殖和下调PHLPP蛋白的表达  

AG490 Inhibits the Proliferation of K562 and Down-regulates Protein Phosphatase PHLPP Expression

作　　者：闫朝奇[1] 张丽君[1] 

机构地区：[1]中国医科大学附属第一医院血液科,辽宁沈阳110001

出　　处：《中国实验血液学杂志》2012年第4期889-892,共4页Journal of Experimental Hematology

摘　　要：本研究旨在探讨AG490抑制K562细胞增殖并诱导其凋亡过程中p-Akt及PHLPP表达的变化。以不同浓度的AG490作用于人慢性髓系急性红白血病细胞株K562,采用WST-1法检测细胞的增殖活性,AnnexinⅤ-FITC双染检测细胞凋亡,Western blot检测p-Akt、Akt、PHLPP蛋白表达水平的变化。结果表明,AG490以时间及浓度依赖性方式抑制K562细胞增殖,其48 h的IC50值为338.0μmol/L;AG490 100μmol/L诱导K562细胞凋亡,呈明显的时间依赖性;AG490 100μmol/L作用于K562细胞后p-Akt及其调节蛋白PHLPP的表达水平呈时间依赖性方式下降,但是对总Akt的表达水平无明显影响。结论:AG490可能通过下调p-Akt的表达抑制K562细胞增殖并诱导其凋亡,但同时也可能通过下调p-Akt的调节蛋白PHLPP的表达水平而使AG490对K562增殖的抑制效果受限。This study was aimed to investigate the effect of AG490 ,a JAK2 inhibitor, on expression of PHLPP and p-Akt in K562. K562 cells were treated with different concentrations of AG490. The proliferation of K562 cells was examined by WST-I assay and apoptosis of K562 cells was detected by flow cytometry with Annexin V -FITC/PI double staining. The expressions of PHLPP, phosphorate-Akt（p-Akt）and total Akt protein were detected by Western blot. The results indicated that AG490 inhibited the proliferation of K562 cells in concentration-and time-dependent manners, with the IC50 338.0 μmol/L in 48 h. AG490 100 μmol/L also induced apoptosis of K562 cells in a time-dependent manner. AG490 100 μmol/L time-dependently down-regulated the protein expression of p-Akt and PHLPP, but without significant effect on expression of total Akt. It is concluded that AG490 can inhibit proliferation and induce apoptosis of K562 ceils through down-regulation of p-Akt expression, but inhibiting efficacy of AG490 on K562 proliferation also may be limited due to the down-regulation of p-Akt regulatory protein PHLPP expression.

关 键 词：AG490 慢性粒细胞白血病 磷酸化AKT PHLPP 细胞凋亡 

分 类 号：R733.72[医药卫生—肿瘤] R979.1[医药卫生—临床医学]