药学学报, 2018, 53(3): 403-409
引用本文:
杨艳芳, 孟盈盈, 叶军, 夏学军, 李琳, 董武军, 王洪亮, 刘玉玲. 模拟体内肿瘤微环境的乳腺癌细胞与脐静脉内皮细胞的体外共培养[J]. 药学学报, 2018, 53(3): 403-409.
YANG Yan-fang, MENG Ying-ying, YE Jun, XIA Xue-jun, LI Lin, DONG Wu-jun, WANG Hong-liang, LIU Yu-ling. Co-culture of human breast adenocarcinoma cells and human umbilical vein endothelial cells to mimic in vivo tumor microenvironment[J]. Acta Pharmaceutica Sinica, 2018, 53(3): 403-409.

模拟体内肿瘤微环境的乳腺癌细胞与脐静脉内皮细胞的体外共培养
杨艳芳, 孟盈盈, 叶军, 夏学军, 李琳, 董武军, 王洪亮, 刘玉玲
中国医学科学院、北京协和医学院药物研究所, 北京 100050
摘要:
为了更好地模拟体内肿瘤组织复杂的微环境特点,本研究采用间接共培养的方法,构建了乳腺癌细胞(human breast adenocarcinoma cells,MCF-7)和人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVECs)的体外共培养模型,以用于后续抗血管生成和诱导肿瘤凋亡的双重疗法的体外研究。分别以同期单独培养的MCF-7和HUVECs细胞为对照,对共培养的MCF-7和HUVECs细胞在培养过程中的细胞活性、形态、电阻、周期和血管内皮生长因子(VEGF)含量进行了考察。结果显示,与单独培养的MCF-7和HUVECs细胞相比,共培养的两种细胞活性更高,且发生了变形、结构变疏松的形貌改变,表现出更低的电阻值,细胞周期活跃、增殖明显(S和G2/M期比例较大),以及有更高的VEGF表达(约1.4~2倍)。该模型很好地模拟了体内肿瘤细胞与肿瘤血管的相互作用关系,可作为设计肿瘤靶向释药系统的体外研究模型。
关键词:   
Co-culture of human breast adenocarcinoma cells and human umbilical vein endothelial cells to mimic in vivo tumor microenvironment
YANG Yan-fang, MENG Ying-ying, YE Jun, XIA Xue-jun, LI Lin, DONG Wu-jun, WANG Hong-liang, LIU Yu-ling
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Abstract:
The development of tumor tissue is a complicated process, which is closely related to tumor microenvironment. In order to simulate the tumor tissue in vivo, non-contact co-culture of human breast adenocarcinoma cells (MCF-7 cells) and human umbilical vein endothelial cells (HUVECs cells) using transwell cell culture plate was developed in this study. The cell viability, morphology, cell resistance, cell cycle and vascular endothelial growth factor (VEGF) protein content of co-cultured MCF-7 and HUVECs cells were investigated, and compared with those of separately cultivated MCF-7 and HUVECs cells during the same period. Different to the separately cultured MCF-7 and HUVECs cells, co-cultured MCF-7 and HUVECs cells exhibited higher cell viability, deformed cell morphology, lower cell resistance, higher proportion of S and G2/M phases and higher VEGF protein content (about 1.4−2 times). The double cell model via non-contact co-culture of MCF-7 and HUVECs cells constructed in this study could simulate the interaction between tumor cells and tumor vascular endothelial cells in vivo, which may provide a more realistic model for subsequent study of drug release system in the control of breast cancer in vitro.
Key words:   
收稿日期: 2017-12-04
DOI: 10.16438/j.0513-4870.2017-1205
基金项目: 国家自然科学基金资助项目(81402874);北京市自然科学基金资助项目(7162135);协和青年基金资助项目(3332015139,2017350020);中国博士后基金资助项目(2017M620679).
通讯作者: 刘玉玲,Tel:86-10-63159373,E-mail:ylliu@imm.ac.cn
Email: ylliu@imm.ac.cn
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