Meyer Paul N, Roychowdhury Shantanu, Kini Ameet R, Alkan Serhan
Loyola University Medical Center, Department of Pathology, 2160 S First Avenue, Maywood, IL 60153, USA.
Leuk Res. 2008 Jan;32(1):143-9. doi: 10.1016/j.leukres.2007.05.009. Epub 2007 Jul 6.
The effects of a novel heat shock protein inhibitor, 17AAG, on established APL cell lines (NB4 and R1) were analyzed. 17AAG induces apoptosis in APL cell lines both sensitive (NB4) and resistant (R1) to ATRA after 72 h of incubation. Apoptosis occurs by a mechanism different than ATRA-mediated response, as the cells do not undergo differentiation before apoptosis. Analysis of bax and bcl-2 shows that pro-apoptotic (bax) and anti-apoptotic (bcl-2) proteins are decreased in expression after incubation with 17AAG. We believe this data supports potential clinical use of agents that target HSP90 in APL patients failing conventional therapy.
分析了一种新型热休克蛋白抑制剂17AAG对已建立的急性早幼粒细胞白血病（APL）细胞系（NB4和R1）的作用。孵育72小时后，17AAG可诱导对全反式维甲酸（ATRA）敏感（NB4）和耐药（R1）的APL细胞系发生凋亡。凋亡通过一种不同于ATRA介导反应的机制发生，因为细胞在凋亡前不会发生分化。对bax和bcl-2的分析表明，与17AAG孵育后，促凋亡蛋白（bax）和抗凋亡蛋白（bcl-2）的表达均降低。我们认为，这些数据支持在常规治疗失败的APL患者中使用靶向HSP90的药物的潜在临床应用。
