Autophagy induced by FTY720 promotes apoptosis in U266 cells
- 作者：Aijun Liao ; Rong Hu ; Qihui Zhao ; Jia Li ; Yingchun Li ; Kun Yao ; Rong Zhang ; Huihan Wang ; Wei Yang ; Zhuogang Liu ; liuzg@sj-hospital.org
- 关键词：FTY720 ; Multiple myeloma ; Apoptosis ; Autophagy ; Reactive oxygen species
- 刊名：European Journal of Pharmaceutical Sciences
- 出版年：2012
- 期刊代码：15_09280987
- 类别：pha
- 出版时间：11 April, 2012
- 卷：45
- 期：5
- 页码：600-605
- 文件大小：692 K
摘要
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.