Page 22 - 南京医科大学学报自然科学版

南京医科大学学报（自然科学版） 第42卷第12期
·1658 · Journal of Nanjing Medical University（Natural Sciences） 2022年12月

·肿瘤专题研究·

胶质瘤干细胞来源的外泌体促进胶质瘤恶性进展

高健成，陆晨飞，张梓枫，张军霞，尤永平 *

南京医科大学第一附属医院神经外科，江苏 南京 210029

［摘 要］ 目的：探讨胶质瘤干细胞（glioblastoma stem cell，GSC）来源的外泌体（extracellular vesicle，EV）对胶质瘤细胞的增
殖、侵袭和替莫唑胺（temozolomide，TMZ）耐药能力的体内外影响。方法：选用原代GSC，通过分化实验获得相对应的分化肿瘤
细胞（differentiated glioma cell，DGC）。通过超速离心法分别获得GSC和DGC细胞培养基上清液中的EV。利用CCK8和克隆形
成实验、transwell侵袭实验检测GSC来源的EV对胶质瘤U87细胞增殖、TMZ耐药和侵袭能力的影响。小鼠颅内原位成瘤实验
分析GSC来源的EV对U87细胞体内增殖、TMZ耐药的影响。结果：通过对原代GSC进行分化，获得了与之相对应的DGC，并
且成功获得GSC和DGC来源EV。与DGC来源的EV相比，GSC来源的EV可显著增强U87细胞增殖、侵袭和替莫唑胺耐药能
力。体内实验进一步证实，GSC来源的EV能显著促进肿瘤体内生长，明显降低小鼠存活期。结论：GSC来源的EV增强胶质瘤
细胞的增殖、侵袭和替莫唑胺耐药能力。
［关键词］ 胶质瘤；肿瘤干细胞；肿瘤微环境；替莫唑胺耐药
［中图分类号］ R739.41 ［文献标志码］ A ［文章编号］ 1007⁃4368（2022）12⁃1658⁃06
doi：10.7655/NYDXBNS20221203

Glioblastoma stem cell⁃derived exosomes promote glioma malignant progression
*
GAO Jiancheng，LU Chenfei，ZHANG Zifeng，ZHANG Junxia，YOU Yongping
Department of Neurosurgery，the First Affiliated Hospital of Nanjing Medical University，Nanjing 210029，China

［Abstract］ Objective：To investigate the effects of extracellular vesicles（EVs）from glioblastoma stem cells（GSC）on the
proliferation，invasion and temozolomide（TMZ）⁃ resistance of glioblastoma（GBM）in vitro and in vivo. Methods：The GSCs were
derived from the primary GBM patient and the matched differentiated glioma cells（DGCs）were obtained through differentiation
experiments. The EVs in culture medium of GSC and DGC were obtained by ultracentrifugation，respectively. Cell Counting Kit 8
（CCK8）assay，colony formation assay and transwell invasion assay were used to detect the effects of GSC ⁃ derived EVs on the
proliferation，invasion and TMZ⁃resistance of U87 glioma cells. Intracranial xenografts murine experiment was used to validate the
effects of GSC⁃derived EVs on the in vivo proliferation，invasion and TMZ⁃resistance of U87 cells. Results：GSC and the matched DGC
were obtained through tumor dissociation and differentiation experiments，respectively. GSC and DGC derived EVs were obtained by
ultracentrifugation methods. GSC⁃derived EVs significantly enhanced U87 cell proliferation，invasion and TMZ⁃resistance，compared to
DGC⁃derived EVs. Consistently，in vivo experiments validated that GSC⁃derived EVs promoted tumor growth and reduced the survival
time of mice. Conclusion：GSC⁃derived EVs enhance the proliferation，invasion and TMZ⁃resistance of glioma cells.
［Key words］ glioma；cancer stem cells；tumor microenvironment；TMZ resistance
［J Nanjing Med Univ，2022，42（12）：1658⁃1663］

胶质母细胞瘤（glioblastoma，GBM）是最常见的 极易复发等特点，严重影响了患者的生存质量 ［1-2］ 。
原发性颅内恶性肿瘤，存在异质性强、放化疗耐药和 胶质瘤干细胞（glioblastoma stem cell，GSC）是具有无
限增殖和自我更新能力的肿瘤细胞亚群，参与了胶

［基金项目］ 国家自然科学基金（81974389） 质瘤恶性进展的众多过程，包括放疗抗性、化疗耐
∗ 药性、血管生成、侵袭和复发等 ［3-4］
通信作者（Corresponding author），E⁃mail：YYPL9@njmu.edu.cn 。外泌体（extra⁃