药学学报, 2019, 54(3): 463-468
王庆华, 付琛, 李晓荣, 侯伊雪, 付爱玲. 外源线粒体抑制小鼠皮下黑色素瘤的生长及机制研究[J]. 药学学报, 2019, 54(3): 463-468.
WANG Qing-hua, FU Chen, LI Xiao-rong, HOU Yi-xue, FU Ai-ling. Mechanism of melanoma growth inhibition by exogenous mitochondria[J]. Acta Pharmaceutica Sinica, 2019, 54(3): 463-468.

王庆华1,2, 付琛1, 李晓荣1, 侯伊雪1, 付爱玲1
1. 西南大学药学院, 重庆 400762;
2. 西南大学动物科学学院, 重庆 402460
肿瘤线粒体结构和功能的改变,可使肿瘤细胞在其缺氧和酸性的微环境中存活并增殖。然而,正常线粒体对肿瘤发生发展的作用尚不清楚。本研究将从安乐死(颈椎快速脱臼处死)后的小鼠肝脏中分离的线粒体静脉注射到荷黑色素瘤小鼠体内(本动物实验经西南大学实验动物伦理审查委员会批准),结果证明外源线粒体可极显著抑制肿瘤细胞的生长,特别是青年小鼠肝脏中分离的线粒体比老年小鼠中分离的线粒体更具抗黑色素瘤效能,肿瘤平均体积从1.35 cm3显著降到0.34 cm3,并且肿瘤平均质量从0.63 g显著降到0.22 g。其抑瘤的机制可能与外源线粒体在黑色素瘤细胞内,诱导线粒体自噬和细胞坏死有关。由于线粒体治疗(mitotherapy)可促进体细胞存活并已应用于临床,因此本研究证明的正常外源线粒体的抗肿瘤作用,有望将外源线粒体治疗作为一种抗肿瘤的治疗方法,还能使人们更深入理解外源线粒体在抗肿瘤中的应用前景。
Mechanism of melanoma growth inhibition by exogenous mitochondria
WANG Qing-hua1,2, FU Chen1, LI Xiao-rong1, HOU Yi-xue1, FU Ai-ling1
1. College of Pharmaceutical Science, Southwestern University, Chongqing 400762, China;
2. College of Animal Science, Southwestern University, Chongqing 402460, China
Alterations of mitochondrial structure and function in tumor cells allow cell survival and proliferation under hypoxic and acidic microenvironment. The effect of normal mitochondria on tumor initiation and development remains unknown. In this study, mice were euthanized by rapid cervical dislocation for isolation of hepatic mitochondria, which were injected intravenously to melanoma-bearing mice. This animal experiment had been approved by Southwest University Experiment Animal Ethics Review Committee. The results showed that exogenous mitochondria can significantly inhibit the growth of melanoma. Mitochondria isolated from the liver of young mice had more potent anti-melanoma effect than those isolated from aging mice. The average volume of tumors decreased significantly from 1.35 cm3 to 0.34 cm3, and the average mass of tumors decreased significantly from 0.63 g to 0.22 g. This anti-tumor mechanism might be associated with induction of mitophagy and cell necrosis after the exogenous mitochondria entering the melanoma cells. As mitotherapy can clinically improve somatic cell survival for treatment of pediatric patients with myocardial ischemia, the observed anti-tumor effect of exogenous mitochondria provides a hope for selective tumor treatment.
Key words:   
收稿日期: 2018-10-25
DOI: 10.16438/j.0513-4870.2018-0968
基金项目: 国家自然科学基金资助项目(81273416);重庆市基础科学和前沿项目(cstc2018jcyjAX0612);重庆市社会与民生保障项目资助(cstc2018jscx-msybX0304).
通讯作者: 付爱玲
Email: fal@swu.edu.cn
PDF(1002KB) Free

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