Flavopiridol, a cyclin-dependent kinase inhibitor (CDKI), shows promising anti-tumor activity in hematologic malignancies. However, Flavopiridol-induced protective autophagy may lead to drug resistance. Here we found that Hsp90 inhibitor 17-AAG can sensitize mantle cell lymphoma (MCL) cells to flavopiridol by suppressing flavopiridol-triggered protective autophagy. The suppressing effect of 17-AAG on autophgy was mediated by Beclin1 degradation and ERK inactivation. Furthermore, 17-AAG enhanced flavopiridol-induced apoptosis and growth suppression in MCL cells. Our study may provide some insights into CDKI -targeted chemotherapies.
基金：
Natural Science Foundation of Hubei Province [2012FFB02435]; [2013QN191]
第一作者单位：[1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Hematol, Wuhan 430030, Peoples R China
通讯作者：
推荐引用方式(GB/T 7714)：
Xiao Y.,Guan J..17-AAG enhances the cytotoxicity of flavopiridol in mantle cell lymphoma via autophagy suppression[J].NEOPLASMA.2015,62(3):391-397.doi:10.4149/neo_2015_047.
APA：
Xiao, Y.&Guan, J..(2015).17-AAG enhances the cytotoxicity of flavopiridol in mantle cell lymphoma via autophagy suppression.NEOPLASMA,62,(3)
MLA：
Xiao, Y.,et al."17-AAG enhances the cytotoxicity of flavopiridol in mantle cell lymphoma via autophagy suppression".NEOPLASMA 62..3(2015):391-397
