Autophagy induced by FTY720 promotes apoptosis in U266 cells
Autophagy induced by FTY720 promotes apoptosis in U266 cells
复制标题
DOI：
10.1016/j.ejps.2011.12.014
复制
发表时间：
2012-04-11
影响因子：
4.6
通讯作者：
Liu, Zhuogang
中科院分区：
文献类型：
--
作者：
Liao, Aijun;Hu, Rong;Liu, Zhuogang
尽管最近的治疗进展，多发性骨髓瘤（MM）仍然无法治愈，患者发展为进行性复发疾病，随后预后不良。已有研究表明FTY 720对包括MM在内的多种血液系统恶性肿瘤具有抗肿瘤活性，但尚未见FTY 720诱导MM细胞自噬的报道。我们观察到FTY 720可诱导U266细胞凋亡，并呈剂量和时间依赖性。FTY 720通过下调抗凋亡蛋白Mcl-1、bcl-2、survivin和Bid的裂解而诱导细胞凋亡。有趣的是，FTY 720诱导自噬，这可能促进U266细胞的凋亡。此外，活性氧（ROS）的活化调节FTY 720诱导的U266细胞凋亡和自噬。该研究表明，FTY 720可能是MM治疗的良好候选药物。(C)出版社：Elsevier B. V.
Despite recent treatment advances, multiple myeloma (MM) remains incurable and patients develop a progressively relapsing disease with subsequent poor prognosis. Studies have shown FTY720 has activities against a number of hematological malignancies including MM, no reports about autophagy induced by FTY720 in MM. Therefore, we investigated the potential application of FTY720 on MM using U266 cell line. We observed that FTY720 could induce caspase-3 dependent apoptosis in a dose- and time-dependent manner in U266 cells. FTY720 caused apoptosis by down-regulating antiapoptotic proteins Mcl-1, bcl-2, survivin and cleavage of Bid. Interestingly, FTY720 induce autophagy which could promote the apoptosis in U266 cells. Furthermore, activation of reactive oxygen species (ROS) regulates FTY720 induced apoptosis and autophagy in U266 cells. The study implicated that FTY720 could be a good candidate for MM treatment. (C) 2012 Published by Elsevier B.V.