Lin Shengyun, Li Jing, Zhou Wenjing, Qian Wenbin, Wang Bo, Chen Zhi
Department of Hematology, The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China.
Institute of Hematology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
Exp Ther Med. 2014 Jun;7(6):1539-1544. doi: 10.3892/etm.2014.1651. Epub 2014 Mar 28.
The novel orally available inhibitor of the molecular chaperone heat shock protein 90 (Hsp90), BIIB021, induces the apoptosis of various types of tumor cell and . However, the effects and mechanisms of this agent on myelodysplastic syndrome (MDS) cell lines remain unknown. The aim of this study was to investigate the effects of BIIB021 on SKM-1 cells (a MDS cell line) and examine its mechanisms of action. The results showed that BIIB021 inhibited the growth of SKM-1 cells effectively . The treatment of SKM-1 cells with BIIB021 resulted in the inhibition of cell growth through G0/G1-phase cell cycle arrest and induced apoptosis by activating caspase-3, -8 and -9. Furthermore, this study also demonstrated that the mechanisms of apoptosis in SKM-1 cells were associated with the suppression of the phosphatidylinositide 3-kinase/Akt and nuclear factor-κB signaling pathways. Therefore, the findings indicate a novel approach for the treatment of high-risk MDS.
新型分子伴侣热休克蛋白90（Hsp90）口服可用抑制剂BIIB021可诱导多种类型肿瘤细胞凋亡。然而，该药物对骨髓增生异常综合征（MDS）细胞系的作用及机制尚不清楚。本研究旨在探讨BIIB021对SKM-1细胞（一种MDS细胞系）的影响并研究其作用机制。结果表明，BIIB021能有效抑制SKM-1细胞的生长。用BIIB021处理SKM-1细胞可通过G0/G1期细胞周期阻滞抑制细胞生长，并通过激活半胱天冬酶-3、-8和-9诱导细胞凋亡。此外，本研究还表明，SKM-1细胞的凋亡机制与磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/Akt）和核因子-κB信号通路的抑制有关。因此，这些发现为高危MDS的治疗指明了一种新方法。
