c-Met inhibitor SU11274 enhances the response of the prostate cancer cell line DU145 to ionizing radiation
c-Met inhibitor SU11274 enhances the response of the prostate cancer cell line DU145 to ionizing radiation
复制标题
c-Met 抑制剂 SU11274 增强前列腺癌细胞系 DU145 对电离辐射的反应
DOI：
10.1016/j.bbrc.2012.09.117
复制
发表时间：
2012-10-26
影响因子：
3.1
通讯作者：
Zhou, Demin
中科院分区：
文献类型：
--
作者：
Yu, Hongliang;Li, Xiaoying;Zhou, Demin
激素难治性前列腺癌对大多数常规治疗（包括放射治疗）表现出实质性抵抗，构成了治愈该疾病患者的关键障碍。c-Met过表达在前列腺癌的发生和疾病进展中起关键作用。在这里，我们证明了SU 11274抑制c-Met可以显着抑制细胞存活和增殖，以及增强DU 145细胞的放射敏感性。SU 11274对DU 145细胞作用的潜在机制可能包括抑制c-Met信号传导、线粒体膜电位去极化、损伤DNA修复功能、消除细胞周期停滞和促进细胞死亡。我们的研究是第一个显示c-Met抑制与电离辐射相结合治疗难治性前列腺癌的有效性。(C)2012 Elsevier Inc. All rights reserved.
Hormone-refractory prostate cancer shows substantial resistance to most conventional therapies including radiotherapy, constitutes a key impediment to curing patients with the disease. c-Met overexpression plays a key role in prostate cancer tumorigenesis and disease progression. Here, we demonstrate that c-Met inhibition by SU11274 could significantly suppress cell survival and proliferation as well as enhance the radiosensitivity of DU145 cells. The underlying mechanisms of the effects of SU11274 on DU145 cells may include the inhibition of c-Met signaling, depolarization of the mitochondrial membrane potential, impairment of DNA repair function, abrogation of cell cycle arrest, and enhancement of cell death. Our study is the first to show the effectiveness of combining c-Met inhibition with ionizing radiation to cure hormone-refractory prostate cancer. (C) 2012 Elsevier Inc. All rights reserved.