Wang Ruo-Tian, Zhi Xiu-Yi, Zhang Yi, Zhang Jian
Department of Thoracic Surgery, Xuanwu Hospital of Capital Medical University (CMU), Beijing 100053, P.R. China.
Exp Ther Med. 2013 Oct;6(4):1054-1058. doi: 10.3892/etm.2013.1259. Epub 2013 Aug 8.
Lung cancer is one of the most common and lethal types of malignancy. To date, radiotherapy and chemotherapy have been used as the two major treatment methods. However, radioresistance of lung cancer remains a therapeutic hindrance. The aim of this study was to identify whether small ubiquitin-related modifier (SUMO)-specific protease 1 (SENP1) is a marker of radioresistance that may serve as a target for enhancing the efficacy of lung carcinoma radiotherapy. SENP1 was observed to be overexpressed in lung cancer tissues, and the modulation of SENP1 expression was demonstrated to significantly affect the proliferation of lung cancer cells. Moreover, silencing the expression of SENP1 using small interfering RNA (siRNA) significantly sensitized lung cancer cells to radiation. Mechanically, it was demonstrated that SENP1 depletion significantly enhanced ionizing radiation (IR)-induced cell cycle arrest, γ-H2AX expression and apoptosis. Thus, these data suggest that SENP1 may be a desirable drug target for lung carcinoma radiotherapy.
肺癌是最常见且致命的恶性肿瘤类型之一。迄今为止,放疗和化疗一直是两种主要的治疗方法。然而,肺癌的放射抗性仍然是治疗的一个障碍。本研究的目的是确定小泛素相关修饰物(SUMO)特异性蛋白酶1(SENP1)是否为放射抗性的标志物,其可能作为增强肺癌放疗疗效的靶点。观察到SENP1在肺癌组织中过表达,并且SENP1表达的调节被证明会显著影响肺癌细胞的增殖。此外,使用小干扰RNA(siRNA)沉默SENP1的表达可显著使肺癌细胞对辐射敏感。从机制上讲,已证明SENP1的缺失会显著增强电离辐射(IR)诱导的细胞周期停滞、γ-H2AX表达和细胞凋亡。因此,这些数据表明SENP1可能是肺癌放疗的理想药物靶点。