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Autophagy induced by FTY720 promotes apoptosis in U266 cells

机译:FTY720诱导的自噬促进U266细胞凋亡

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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.
机译:尽管最近有治疗进展,但多发性骨髓瘤(MM)仍无法治愈,患者会发展为复发性疾病,且预后较差。研究表明FTY720对包括MM在内的许多血液系统恶性肿瘤具有活性,尚无关于FTY720在MM中诱导自噬的报道。因此,我们使用U266细胞系研究了FTY720在MM中的潜在应用。我们观察到,FTY720可以在U266​​细胞中以剂量和时间依赖性方式诱导caspase-3依赖性凋亡。 FTY720通过下调抗凋亡蛋白Mcl-1,bcl-2,survivin和Bid的切割而引起凋亡。有趣的是,FTY720诱导自噬可以促进U266细胞凋亡。此外,活性氧(ROS)的激活可调节FTY720诱导的U266细胞凋亡和自噬。该研究暗示FTY720可能是MM治疗的良好候选者。

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