基于微流控芯片构建三维基质支架中的多细胞球体模型

抗癌药物在进行动物和临床试验以前,需要用体外肿瘤组织模型评估药效.由于三维(3D)多细胞球体(multicellular tumor spheroids MCTSs)在抗药性和组织结构等方面与体内肿瘤组织相似,常被用作体外肿瘤组织模型.为监测MCTSs在形成过程中,肿瘤细胞之间和肿瘤细胞与基质之间的相互作用,基于微流控技术基础上自行设计和构建MCTSs模型.该肿瘤MCTSs模型实验结果表明,在3D微环境下,血清能够诱导MDA-MB-231形成直径为289μm的MCTSs,肿瘤细胞MCTSs之间有相互靠近的趋势,并且发现凋亡细胞多分布在MCTSs之间.肿瘤坏死因子(tumor necrosis factor-α,TNF-α)诱导MDA-MB-231形成MCTSs之间没有相互靠近的趋势,并且MCTSs直径的长度很难达到100μm.以上结果表明,该模型有望为研究肿瘤形成MCTSs机制和药物筛选提供有用的体外肿瘤模型.

A Novel Multicellular Tumor Spheroids Model Based on a Microfludic Device in 3D Matrix

Development of cancer therapeutics requires a thorough evaluation of drug efficacy in vitro before animal testing and subsequent clinical trials.Multicellular tumor spheroids(MCTSs) resemble real tissues better in terms of drug resistance and structural,MCTSs formed by transformed cells are widely used as avascular tumor models for therapeutic screening.A novel invasion model in vitro was created.In contrast to the traditional methods,this model could be better to simulate extracellular matrix for MCTSs,to track the process of MCTSs and to observe the tumor cell-extracellular matrix interaction.The results showed that MDA-MB-231 were so easy to aggregate and form MCTSs in 3D extracellular matrix,there was a blending tendency with MCSs.TNF-α affects the aggregation properties of MDA-MB-231 cells into MCTSs,and the MCTSs was smaller than 100 μm in diameter.These data suggested that the MCTSs model might serve as a useful in vitro system for screening cancer therapeutics.