Cancer metastasis is one of the most serious problems for tumor therapy, which is closely related to cell adhesion and deadhesion process. Better comprehension of cell adhesion ability will benefit drug research. Here, a biomimetic microfluidic enzyme digestion method was proposed to gently measure the influence of drugs on cell-matrix adhesion ability at the single cell level. The method can selectively digest the extracellular matrix (ECM) that linked to a single cell, and the trypsin concentration around the cell is relatively uniform and constant, thus the measured cell adhesion strength should be precise. Commercially available anti-cancer agents including 5-fluorouracil (5-FU), actinomycin D (Act D), temozolomide (TMZ) and allicin were evaluated, and the data showed only TMZ and allicin can inhibit cell adhesion significantly under our experiment conditions. The influence of TMZ became more and more obvious as the increase of duration and the effect became prominent only after 6 h adhesion process, which could provide a quick evaluation of whether the drugs are effective to cancer cell (compared with Calcein-AM/PI cell viability test). The adhesion strength of U87 cells decreased when the concentration of TMZ increased, and the effect of TMZ can be effectively inhibited by adding lactic acid to culture medium, which indicated acidic tumor microenvironment could promote drug resistance of tumor cells. Different from conventional evaluation methods which focus on the drugs’ influence on cellular viability or metabolism, this work provides a new perspective to study the effect of drugs, which is helpful to enrich the drug evaluation system.

癌症转移是肿瘤治疗中最严重的问题之一，其与细胞粘附和粘连过程密切相关。更好地理解细胞粘附能力将有益于药物研究。在此，提出了一种仿生微流酶消化方法，以在药物单细胞水平上温和地测量药物对细胞基质粘附能力的影响。该方法可以选择性消化连接到单个细胞的细胞外基质（ECM），并且细胞周围的胰蛋白酶浓度相对均匀且恒定，因此测量的细胞粘附强度应精确。对包括5-氟尿嘧啶（5-FU），放线菌素D（Act D），替莫唑胺（TMZ）和大蒜素的市售抗癌药进行了评估，数据显示，在我们的实验条件下，只有TMZ和大蒜素能显着抑制细胞粘附。TMZ的影响随着持续时间的增加而变得越来越明显，并且仅在粘附后6小时才显着，这可以快速评估药物是否对癌细胞有效（与Calcein-AM / PI细胞相比）生存力测试）。随着TMZ浓度的增加，U87细胞的黏附强度降低，向培养基中添加乳酸可以有效抑制TMZ的作用，说明酸性肿瘤微环境可以促进肿瘤细胞的耐药性。与专注于药物对细胞生存力或代谢的影响的常规评估方法不同，这项工作为研究药物的作用提供了新的视角，