王华伟 王华南 康肖梦 张宇睿 杨福军 徐文清（中国医学科学院 北京协和医学院放射医学研究所 天津分子核医学重点实验室 天津 300192）



线粒体靶向抗氧化剂MitoQ的抗肿瘤效应

王华伟 王华南 康肖梦 张宇睿 杨福军 徐文清
（中国医学科学院 北京协和医学院放射医学研究所 天津分子核医学重点实验室 天津 300192）

摘要采用噻唑蓝(MTT)法检测不同浓度MitoQ对肝癌HepG2细胞的毒性；凋亡诱导实验研究不同浓度MitoQ对HepG2细胞凋亡率的影响；裸鼠移植瘤模型研究MitoQ对肝癌HepG2荷瘤小鼠的抑瘤作用。结果表明，MitoQ对肝癌HepG2细胞的抑制作用随着浓度而增加；给药组凋亡率显著高于对照组(p<0.01)；MitoQ在1、5、10 mg/kg 剂量给药10 d后对小鼠的肿瘤生长均有抑制作用，与对照组相比，10 mg/kg剂量组肿瘤体积(p<0.01)和肿瘤质量(p<0.05)均有显著性差异。结果提示，MitoQ在体内体外均具有抑制肝癌HepG2细胞生长的作用。

关键词MitoQ，抗肿瘤，HepG2细胞，细胞凋亡，线粒体靶向

Supported by Tianjin Research Program of Application Foundation and Advanced Technology(14JCZDJC36400), Beijing Union

Medical College Youth Fund(33320140124), and the Institute of Radiation Medicine, Chinese Academy of Medical Sciences

Research Fund(1555)

First author: WANG Huawei, male, was born in September 1988 and graduated from Henan University in 2012. Now he is a master candidate of the Institute of Radiation Medicine, Chinese Academy of Medical Sciences

Received 11 September 2015; accepted 08 October 2015

Anti-tumor effects of mitochondria targeted antioxidant MitoQ

WANG Huawei WANG Huanan KANG Xiaomeng ZHANG Yurui YANG Fujun XU Wenqing
(Tianjin Key Laboratory of Molecular Nuclear Medicine, Perking Union Medicine College & Chinese Academy of Medical Sciences, Institute of Radiation Medicine, Tianjin 300192, China)

ABSTRACT MTT was used to detect the cell toxicity of different concentrations of MitoQ on liver cancer HepG2 cells. Apoptosis-inducing assay was used to detect the apoptosis rate on liver cancer HepG2 cells after the treatment with varying MitoQ concentrations. Xenograft tumor model assay was used to investigate the anti-tumor effects of MitoQ on HepG2 hepatocarcinoma-bearing mice. The results showed that the inhibitory effects of MitoQ on HepG2 cells increased with MitoQ concentration, and compared with control group, the administration group apoptosis rate was significantly higher (p<0.01). In nude mice xenograft tumor model assay, the tumor growth was all inhibited after the treatment with 1 mg/kg, 5 mg/kg, and 10 mg/kg MitoQ concentration after 10 d. When the mice were treated with 10 mg/kg MitoQ, tumor volume (p<0.01) and tumor mass (p<0.05) were significantly different from those of the blank group (p<0.01). The results indicate that MitoQ has antitumor effect in vivo and in vitro.

KEYWORDS MitoQ, Auti-tumor, HepG2 cell, Cell apoptosis, Mitochondria targeted

CLC R96

MitoQ是由Murphy和Smith在20世纪90年代设计并合成的线粒体靶向抗氧化剂，它由具有抗氧化作用的辅酶Q和具有靶向作用的三苯基膦组成，两部分通过含10个碳原子的脂肪链链接（见图1）[1-2]。大量体内体外实验表明[3-4]，MitoQ可以较容易地渗透通过细胞膜和线粒体膜，根据能斯特方程，在正常的生物状态下，每61.5 mV的膜电势亲脂阳离子摄入进线粒体增加10倍，所以与一般的辅酶Q相比，MitoQ可以在线粒体中大量积累（是原来的100～1000倍），从而达到保护线粒体免受氧化应激损伤，同时也可调控癌细胞的凋亡通道，达到治疗肿瘤的目的。

有文献报道[2-3, 5]，MitoQ被用于帕金森、局部缺血-再灌注、肌萎缩性脊髓侧索硬化症和线粒体疾病等疾病的治疗。然而，对于MitoQ的抗肿瘤研究尚未见报道，本研究将对其进行初步探索，以期为深入研究提供依据。……