Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.
Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.
Biochem Biophys Res Commun. 2014 Jun 20;449(1):49-54. doi: 10.1016/j.bbrc.2014.04.147. Epub 2014 May 4.
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.
虽然电离辐射 (IR) 已经为鼻咽癌 (NPC) 的治疗提供了相当大的改善，但在某些患者亚群中，放射抗性仍然是治疗中的一个主要问题。在这项研究中，我们证明了照射诱导 MET 的过度表达和激活，以及由肝细胞生长因子 (HGF) 介导的异常 MET 信号诱导了放射抗性。我们还发现，MET 抑制剂 PHA-665752 可有效抑制 NPC 细胞中 HGF 诱导的细胞增殖和放射抗性。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）联合使用可能是 NPC 的一种有前途的治疗策略。
