MET inhibitor PHA-665752 suppresses the hepatocyte growth factor-induced cell proliferation and radioresistance in nasopharyngeal carcinoma cells
MET inhibitor PHA-665752 suppresses the hepatocyte growth factor-induced cell proliferation and radioresistance in nasopharyngeal carcinoma cells
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MET抑制剂PHA-665752抑制肝细胞生长因子诱导的鼻咽癌细胞增殖和放射抗性
DOI：
10.1016/j.bbrc.2014.04.147
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发表时间：
2014-06-20
影响因子：
3.1
通讯作者：
Wang, Wei
中科院分区：
文献类型：
--
作者：
Liu, Tongxin;Li, Qi;Wang, Wei
虽然电离辐射（IR）已经为鼻咽癌（NPC）提供了相当大的改善，但在患者亚群中，放射耐药仍然是治疗中的主要问题。在这项研究中，我们证明了辐照诱导MET过表达和激活，以及由肝细胞生长因子（HGF）介导的异常MET信号诱导辐射抵抗。我们还发现MET抑制剂PHA-665752能有效抑制HGF诱导的鼻咽癌细胞增殖和辐射耐药。进一步的研究表明，PHA-665752以剂量依赖的方式抑制Akt、ERK1/2和STAT3蛋白的磷酸化。我们的数据表明，IR与MET抑制剂（如PHA-665752）的联合治疗可能是一种有希望的鼻咽癌治疗策略。(C) 2014爱思唯尔公司版权所有。
Although ionizing radiation (IR) has provided considerable improvements in nasopharyngeal carcinoma (NPC), in subsets of patients, radioresistance is still a major problem in the treatment. In this study, we demonstrated that irradiation induced MET overexpression and activation, and the aberrant MET signal mediated by hepatocyte growth factor (HGF) induced radioresistance. We also found that MET inhibitor PHA-665752 effectively suppressed HGF induced cell proliferation and radioresistance in NPC cells. Further investigation indicated that PHA-665752 suppressed the phosphorylation of the Akt, ERK1/2, and STAT3 proteins in a dose-dependent manner. Our data indicated that the combination of IR with a MET inhibitor, such as PHA-665752, might be a promising therapeutic strategy for NPC. (C) 2014 Elsevier Inc. All rights reserved.