天津医药

天津医药 ›› 2019, Vol. 47 ›› Issue (6): 600-604.doi: 10.11958/20190736

• 细胞与分子生物学 • 上一篇    下一篇

间充质干细胞来源的外泌体抑制乳腺癌细胞生长的研究

何宁宁1 ， 王津晗1 ， 王彦1 ， 杜利清1 ， 徐畅1 ， 冯宇2 ， 孙晓辉1 ， 蔡慧1 ， 刘强1△   

  1. 1中国医学科学院放射医学研究所 （邮编300192）； 2天津市人民医院呼吸科
  • 收稿日期:2019-03-14 修回日期:2019-04-19 出版日期:2019-06-15 发布日期:2019-06-15
  • 通讯作者: 何宁宁 E-mail:hening1123@126.com
  • 基金资助:
    国家自然科学基金面上项目;国家自然科学基金青年项目;国家自然科学基金青年项目;中国医学科学院医学与健康科技创新工程项目;天津市自然科学基金青年项目;天津市自然科学基金青年项目

Inhibitory effect of exosomes derived from mesenchymal stem cells on the growth of breast cancer cells

HE Ning-ning1 , WANG Jin-han1 , WANG Yan1 , DU Li-qing1 , XU Chang1 , FENG Yu2 , SUN Xiao-hui 1 , CAI Hui 1 , LIU Qiang1△   

  1. 1 Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Molecular Nuclear Medicine, Tianjin 300192, China; 2 Department of Respiratory, Tianjin People's Hospital
  • Received:2019-03-14 Revised:2019-04-19 Published:2019-06-15 Online:2019-06-15

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摘要： 摘要： 目的 研究脐带间充质干细胞来源的外泌体 （MSCs-Exo） 对乳腺癌细胞生长的影响。方法 利用生物发光成像技术的双报告基因 （萤火虫荧光素酶-绿色荧光蛋白， Fluc-GFP） 载体， 通过慢病毒转染构建人乳腺癌MDA- MB-231细胞系 （231-Fluc-GFP）， 以便在体内可以对细胞进行实时监测。分别采用MSCs-Exo （MSCs-Exo组） 和PBS （对照组） 处理细胞， 体外实验对2组细胞进行形态学观察、 增殖、 存活、 STAT3及其下游基因表达的检测； 通过皮下注射2组细胞建立裸鼠体内乳腺癌模型， 对不同处理条件下的细胞成瘤情况进行分析。结果 体外实验结果显示 MSCs-Exo处理后乳腺癌MDA-MB-231细胞增殖受到了抑制， 在处理第3天时2组细胞数差异有统计学意义 （P＜ 0.05）； 处理后细胞存活率降低 （P＜0.01）； 外泌体处理组STAT3及其下游基因C-MYC， BCL-XL， NANOG， OCT4， SOX2 表达下降。体内实验结果显示MSCs-Exo处理组肿瘤细胞在体内的生长受到抑制。结论 脐带间充质干细胞来源的外泌体抑制乳腺癌细胞的生长。

关键词: 间充质基质细胞, 外泌体, 乳腺肿瘤, 发光测定法, 萤光素酶类

Abstract: Abstract: Objective To study the effect of mesenchymal stem cell derived exosomes (MSC-Exo) on the proliferation of breast cancer cells. Methods The human breast cancer cell line MDA-MB-231 (231-Fluc-GFP) was constructed by lentiviral transfection using a double-reporter gene (fluorescein-green fluorescent protein, fluc-GFP) vector based on bioluminescence imaging technology, so that the cells were monitored in vitro in real time. Cells were treated with MSCs-Exo (MSCs-Exo group) and PBS (control group) respectively. The morphological observation, proliferation, survival rate and results of real-time PCR in vitro cells were performed in two groups of cells. In vivo, a nude mouse breast cancer model was established, and the tumor formation under different treatment conditions was analyzed. Results The proliferation of breast cancer MDA-MB-231 cells was inhibited after treatment with mesenchymal stem cell-derived exosomes. There were significant differences in cell numbers on the 3rd day of treatment between the two groups (P＜0.05). The survival rate of breast cancer cells decreased after treatment (P＜0.01). The expression of STAT3 and its downstream genes C-MYC， BCL- XL， NANOG， OCT4 and SOX2 decreased in exosome treatment group. In vivo, the growth of tumor cells treated with MSCs- Exo was inhibited. Conclusion Mesenchymal stem cell-derived exosomes inhibit breast cancer cell growth.

Key words: mesenchymal stromal cells, exosomes, breast neoplasms, luminescent measurements, luciferases