Shen Zetian, Wu Xinhu, Wang Zhen, Li Bing, Zhu Xixu
Department of Radiation Oncology, Jinling Hospital, Medical School of Nanjing University Nanjing 210002, Jiangsu Province, China.
Department of Hyperbaric Oxygen, Jinling Hospital, Medical School of Nanjing University Nanjing 210002, Jiangsu Province, China.
Int J Clin Exp Pathol. 2015 Jan 1;8(1):643-8. eCollection 2015.
The aim of the present study is to investigate whether there is a relationship between miR-18a expression and radiosensitization of non-small-cell lung caner (NSCLC). The relationship between miR-18a expression and clinicopathological characteristics was investigated. To determine whether the miR-18a expression levels were associated with radiotherapeutic efficacy, therapeutic response was evaluated by radiologic Response Evaluation Criteria in Solid Tumors (RECIST). To determine whether miR-18a was required for lung cancer cell radioresistance, A549 cells were treated with different doses of ionizing radiation, following transfection with inhibitor miR-18a or inhibitor NC. We found that the level of miR-18a in NSCLC was strongly correlated with tumor differentiation (P = 0.026), regional lymph node metastasis (P = 0.013) and clinical TNM stage (P = 0.005). According to RECIST, miR-18a expression level was significantly associated with therapeutic response, exhibiting higher expression level in non-responsive patients. Furthermore, the depletion of miR-18a increased A549 cell radiosensitivity. In conclusion, we provide the evidence that down-regulation of miR-18a sensitizes NSCLC to radiation treatment, and it may help to develop a new approach to sensitizing radioresistant lung cancer cells by targeting miR-18a.
本研究的目的是调查miR-18a表达与非小细胞肺癌(NSCLC)放射增敏之间是否存在关联。研究了miR-18a表达与临床病理特征之间的关系。为了确定miR-18a表达水平是否与放射治疗疗效相关,采用实体瘤疗效评价标准(RECIST)评估治疗反应。为了确定miR-18a是否是肺癌细胞辐射抗性所必需的,在用抑制剂miR-18a或抑制剂NC转染后,用不同剂量的电离辐射处理A549细胞。我们发现,NSCLC中miR-18a的水平与肿瘤分化(P = 0.026)、区域淋巴结转移(P = 0.013)和临床TNM分期(P = 0.005)密切相关。根据RECIST,miR-18a表达水平与治疗反应显著相关,在无反应患者中表达水平较高。此外,miR-18a的缺失增加了A549细胞的放射敏感性。总之,我们提供的证据表明,miR-18a的下调使NSCLC对放射治疗敏感,并且它可能有助于开发一种通过靶向miR-18a使放射抗性肺癌细胞敏感的新方法。