利用RNA干扰使EZH2基因沉默可增强辐射诱导的对人肺癌体外和体内生长的抑制作用。
EZH2 silencing with RNAi enhances irradiation-induced inhibition of human lung cancer growth in vitro and in vivo.
作者信息
Xia Hui, Yu Chang-Hai, Zhang Yiming, Yu Jianqi, Li Jie, Zhang Wen, Zhang Baoshi, Li Yingjie, Guo Nannan
机构信息
Department of Cardiothoracic Surgery, First Affiliated Hospital of PLA General Hospital, Beijing 100048, P.R. China.
出版信息
Oncol Lett. 2012 Jul;4(1):135-140. doi: 10.3892/ol.2012.696. Epub 2012 Apr 26.
Abstract
Non-small cell lung cancer (NSCLC) has a high mortality rate and poor prognosis. The aim of the present study was to silence EZH2 and explore the antitumor effect of small interfering RNA (siRNA)-EZH2 in combination with radiotherapy, which is a main treatment for NSCLC. The results showed that irradiation in the presence of siRNA-EZH2 arrested A549 cells in the G(0) and G(1) phases, delayed cell cycle progression and effectively inhibited cell proliferation, compared with cells that received radiotherapy alone. The combined therapy enhanced the percentage of apoptotic A549 cells in vitro and reduced the tumor size, in addition to increasing the survival rate in tumor xenograft experiments. This study demonstrates the antitumor activity of ionizing radiation therapy in combination with siRNA-EZH2 in NSCLC, both in vitro and in vivo, as well as providing a scientific rationale for targeting EZH2 to enhance the sensitivity of cancer to radiotherapy in NSCLC patients.
摘要
非小细胞肺癌（NSCLC）死亡率高且预后不良。本研究的目的是沉默EZH2，并探索小干扰RNA（siRNA）-EZH2与放射治疗联合应用的抗肿瘤作用，放射治疗是NSCLC的主要治疗方法。结果显示，与单独接受放射治疗的细胞相比，在siRNA-EZH2存在的情况下进行照射可使A549细胞停滞在G(0)期和G(1)期，延迟细胞周期进程并有效抑制细胞增殖。联合治疗除了提高肿瘤异种移植实验中的存活率外，还增加了体外凋亡A549细胞的百分比并减小了肿瘤大小。本研究证明了电离辐射疗法与siRNA-EZH2联合应用在NSCLC体外和体内的抗肿瘤活性，同时也为靶向EZH2以提高NSCLC患者癌症对放射治疗的敏感性提供了科学依据。
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