模拟肿瘤微环境的多细胞共培养肿瘤球模型在药物研究中的应用  

Application of a multicellular co-culture tumor spheroid model simulating tumor microenvironment to drug research

作　　者：邢一卓 杨鸿轩 邓仪卿 张宏 XING Yizhuo;YANG Hongxuan;DENG Yiqing;ZHANG Hong(Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;School of Life Sciences,Huaibei Normal University,Huaibei 235000,China)

机构地区：[1]上海中医药大学交叉科学研究院,上海201203 [2]淮北师范大学生命科学学院,淮北235000

出　　处：《中华中医药杂志》2023年第12期5925-5932,共8页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.82174023)。

摘　　要：肿瘤微环境是癌细胞生存的环境,包含多种类型细胞如成纤维细胞、血管内皮细胞、免疫细胞等,以及这些细胞分泌的各种成分,与癌细胞动态相互作用,由此影响肿瘤的生长、转移及最终预后。中药复方具有扶正祛邪和多成分协同作用特点,可通过改善肿瘤微环境而发挥抗癌作用。目前广泛应用的体外单层细胞培养模型难以模拟体内复杂的肿瘤微环境状态,尤其不能反映免疫细胞与癌细胞的相互作用,一定程度阻碍了组分中药的发展。近年发展起来的多细胞共培养肿瘤球(MCCTS)技术,由于能更好地模拟体内肿瘤微环境,适合组分中药配伍研究。MCCTS目前主要以肿瘤细胞与成纤维细胞和/或血管内皮细胞共培养,用于化学药物敏感性、联合应用及纳米渗透作用等的研究,缺乏包含免疫细胞在内的4种以上类型细胞共培养模型,亦鲜见用于中药研究的文献报道。今后应加强包含免疫细胞在内的MCCTS模型构建及在组分中药研究中的应用,以体现中药方剂配伍优势,阐释中医药科学内涵,推动中医药发展。Tumor microenvironment(TME)is the survival environment of cancer cells,containing many types of cells such as fibroblasts,vascular endothelial cells,and immune cells,and various components they secrete themselves.These cells interact dynamically with cancer cells,thereby affecting tumor growth,metastasis and prognosis.Chinese medicine formula plays a synergistic anti-tumor role by improving the TME,which has the characteristics of strengthening vital qi to eliminate pathogenic factor and multi-component synergy.The multicellular co-culture tumor spheroid(MCCTS)model developed in recent years is more suitable for the study of component-comprised Chinese medicine as it can better mimic the TME in vivo.The present article introduces the common types of cells in the TME,their effects in cancer progression,and the applications of multicellular tumor spheroid models in drug research.Currently,MCCTS mainly comprises tumor cells,fibroblasts and/or vascular endothelial cells.and there is no co-culture of more than four types of cells including immune cells.MCCTS is employed mainly for investigation of the sensitivity,combined application and nano penetration of chemical drugs,but rarely for research of Chinese medicines and natural products.In the future,we should strengthen the construction of MCCTS model containing immune cells and its applications in component-composed Chinese medicine research.It will refect the characteristics and advantages of compatibility and immune regulation of Chinese medicine formula and lay a foundation for explaining the modern scientific connotation of traditional Chinese medicine.

关 键 词：肿瘤球 模型 肿瘤微环境 免疫细胞 组分中药 配伍 科学内涵 

分 类 号：R28[医药卫生—中药学]