Synergistic Effect of TPD7 and Berberine against Leukemia Jurkat Cell Growth through Regulating Ephrin-B2 Signaling
Synergistic Effect of TPD7 and Berberine against Leukemia Jurkat Cell Growth through Regulating Ephrin-B2 Signaling
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TPD7 和小檗碱通过调节 Ephrin-B2 信号传导对白血病 Jurkat 细胞生长的协同作用
DOI：
10.1002/ptr.5866
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发表时间：
2017-09-01
影响因子：
7.2
通讯作者：
Zhang, Yanmin
中科院分区：
文献类型：
--
作者：
Ma, Weina;Zhu, Man;Zhang, Yanmin
TPD 7（一种新型联苯脲塔斯品碱衍生物）和小檗碱对VEGFR 2具有抑制作用，该抑制作用可以通过与PDZ结构域的相互作用由肝配蛋白-B2反向信号传导调节。本研究的目的是研究TPD 7和小檗碱（TAB）联合对T细胞急性淋巴细胞白血病细胞生长的抑制作用。TPD 7和小檗碱一起协同抑制Jurkat细胞的增殖。此外，TAB的组合通过下调细胞周期蛋白D1、细胞周期蛋白E和CDC 2的水平诱导G（1）期细胞周期停滞。此外，TAB的组合显著增强Jurkat细胞的凋亡，并且凋亡最可能是通过调节Bcl-2家族成员的水平而引起的。最重要的是，伴随治疗同时调节ephrin-B2和VEGFR 2信号传导，以及调节MEK/ERK和PTEN/PI 3 K/AKT/mTOR信号传导。因此，TAB的联合治疗可能是治疗T细胞急性淋巴细胞白血病的一种有前途的治疗方法。版权所有（c）2017约翰威利父子有限公司
TPD7, a novel biphenyl urea taspine derivative, and berberine have presented inhibition on VEGFR2 that can be regulated by ephrin-B2 reverse signaling through interactions with the PDZ domain. The purpose of this study is to investigate the inhibitory effect of the combination of TPD7 and berberine (TAB) on T-cell acute lymphoblastic leukemia cell growth. TPD7 and berberine together synergistically inhibited the proliferation of Jurkat cells. Also, the combination of TAB induced G(1)-phase cell-cycle arrest by downregulating the level of cyclin D1, cyclin E, and CDC2. Furthermore, the combination of TAB significantly enhanced apoptosis in Jurkat cells, and the apoptosis most likely resulted from the modulation of the level of Bcl-2 family members. Most importantly, the concomitant treatment simultaneously regulated the ephrin-B2 and VEGFR2 signaling, as well as modulated the MEK/ERK and PTEN/PI3K/AKT/mTOR signaling. Therefore, the combination treatment of TAB may be a promising therapeutic method in treating T-cell acute lymphoblastic leukemia. Copyright (c) 2017 John Wiley & Sons, Ltd.