Chen Xiaohui, Yang Chunmei, Xu Yanhua, Zhou Hui, Liu Hui, Qian Wenbin
Department of Hematology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310015;
Exp Ther Med. 2013 Aug;6(2):299-304. doi: 10.3892/etm.2013.1161. Epub 2013 Jun 14.
The orally active microtubule-depolymerizing agent CYT997 is potently cytotoxic to a variety of tumors and . However, the effects of this agent on acute myeloid leukemia (AML) cells and its mechanisms are unknown. The present study demonstrated that CYT997 effectively inhibited the growth of AML cells . Treatment of AML cells with CYT997 resulted in G2/M phase cell cycle arrest, and induced apoptosis through the activation of extrinsic and intrinsic apoptotic pathways. Furthermore, CYT997 induced cell death in CD123 leukemia cells and significantly reduced leukemia colony formation. CYT997 was also demonstrated to exert dual effects on the expression of PI3K/Akt and mechanistic target of rampamycin (mTOR) signaling pathway proteins. Therefore, CTY997, used alone or in combination with chemotherapy, may represent a promising approach for the treatment of AML.
口服活性微管解聚剂CYT997对多种肿瘤具有强大的细胞毒性。然而，该药物对急性髓系白血病（AML）细胞的作用及其机制尚不清楚。本研究表明，CYT997能有效抑制AML细胞的生长。用CYT997处理AML细胞导致G2/M期细胞周期停滞，并通过激活外源性和内源性凋亡途径诱导凋亡。此外，CYT997诱导CD123白血病细胞死亡，并显著减少白血病集落形成。还证明CYT997对PI3K/Akt和雷帕霉素机制性靶标（mTOR）信号通路蛋白的表达具有双重影响。因此，单独使用或与化疗联合使用CYT997可能是一种有前景的AML治疗方法。
