一种简易的体外分析肿瘤细胞三维迁移行为的医学研究微装置  

A Simple Medical Research Microdevice for Analyzing Three-dimensional Migration of Tumor Cells in Vitro

作　　者：张伟[1] 何婧 伍伦刚 彭现其 李远[1] ZHANG Wei;HE Jing;WU Lungang;PENG Xianqi;LI Yuan(Central Laboratory,Yongchuan Hospital,Chongqing Medical University,Chongqing 402160,China)

机构地区：[1]重庆医科大学附属永川医院中心实验室

出　　处：《中国医学科学院学报》2019年第2期162-169,共8页Acta Academiae Medicinae Sinicae

基　　金：国家自然科学基金(11702047);重庆市博士后科研项目(Xm2017082);重庆医科大学附属永川医院院级重点项目(YJZQN201534);重庆医科大学大学生科学研究和创新实验项目(CXSY201816)~~

摘　　要：目的发展并验证一种体外分析肿瘤细胞在细胞外基质中三维(3D)迁移行为的医学研究微装置。方法利用精密机械加工方法制作微装置模具,通过聚二甲基硅氧烷(PDMS)浇筑、翻模和封装得到基于PDMS-玻璃材质的肿瘤细胞3D迁移分析装置;分析时,将肿瘤细胞悬液和基质胶混匀后加入微装置迁移通道,通过在迁移通道两侧建立趋化因子浓度梯度诱导肿瘤细胞在基质胶中的可控迁移,同时利用活细胞动态成像装置记录肿瘤细胞的迁移过程。结果以乳腺癌细胞株MCF-7为例,验证了该微装置在体外控制和动态监测肿瘤细胞3D迁移过程的可行性;定性分析影像学数据显示MCF-7细胞株在基质胶中迁移受化学诱导剂浓度梯度分布方向决定,且呈变形虫样迁移模式;定量分析细胞迁移过程可量化MCF-7的细胞迁移率和迁移速度,基质金属蛋白酶抑制剂(巴马司他)和三磷酸腺苷酶抑制剂(Blebbistation)对MCF-7细胞3D迁移行为的抑制能力存在差异。结论本装置未来可用于深入解析肿瘤细胞3D迁移行为、机制和抗肿瘤转移药物的药效评估。Objective To develop and verify a medical microdevice for analyzing the three-dimensional(3D)migration of tumor cells in extracellular matrix. Methods The mold of the microdevice was made by precision machining,and then the medical microdevice based on polydimethylsiloxane(PDMS)-glass was obtained by PDMS casting,moulding,and bonding.During the analysis,the suspension of tumor cells and matrigel were mixed and then added into the migration channel of microdevice,and the controllable migration of tumor cells in matrigel was induced by establishing chemokine concentration gradient on both sides of the migration channel.Meanwhile,the migration process of tumor cells was recorded with the live cell dynamic imaging device. Results Breast cancer cell line MCF- 7 was taken as an example to verify the feasibility of the microdevice to control and dynamically monitor the 3D migration process of tumor cells in vitro .Qualitative analysis of imaging data showed that the migration of MCF- 7 cell lines in matrigel was determined by the concentration gradient distribution direction of chemokine and presented as the amoeboid-like migration mode.The proportion and migration velocity of MCF- 7 cells could be quantified by the quantitative analysis of cell migration process.The inhibition ability of matrix metalloproteinase inhibitors(Batimastat)and adenosine triphosphatase inhibitors(Blebbistation)on the 3D migration behavior of MCF- 7 cells was found to be different. Conclusion This device can be used for in-depth analysis of tumor cell migration and its mechanism and for evaluating the efficacy of anti-metastatic drugs.

关 键 词：肿瘤转移 细胞迁移 微装置 基质胶 乳腺癌细胞株MCF-7 

分 类 号：R-331[医药卫生]