Zuchowska Agnieszka, Kwapiszewska Karina, Chudy Michal, Dybko Artur, Brzozka Zbigniew
Department of Microbioanalytics, Institute of Biotechnology, Warsaw University of Technology, Warsaw, Poland.
Institute of Physical Chemistry, Polish Academy of Sciences, Warsaw, Poland.
Electrophoresis. 2017 Apr;38(8):1206-1216. doi: 10.1002/elps.201600417. Epub 2017 Feb 14.
Cell-on-a-chip systems have become promising devices to study the effectiveness of new anticancer drugs recently. Several microdevices for liver cancer culture and evaluation of the drug cytotoxicity have been reported. However, there are still no proven reports about high-throughput and simple methods for the evaluation of drug cytotoxicity on liver cancer cells. The paper presents the results of the effects of the anticancer drug (5-fluorouracil, 5-FU) on the HepG2 spheroids as a model of liver cancer. The experiments were based on the long-term 3D spheroid culture in the microfluidic system and monitoring of the effect of 5-FU at two selected concentrations (0.5 mM and 1.0 mM). Our investigations have shown that the initial size of the spheroids has influence on the drug effect. With the increase of the spheroids diameter, the drug resistance (for the two tested 5-FU concentrations) decreases. This phenomenon was observed both through cells metabolism analysis, as well as changes in spheroids sizes. In our research, we have shown that the lower 5-FU (0.5 mM) concentration causes higher decrease in HepG2 spheroids viability. Moreover, due to the microsystem construction, we observe the drug resistance effect (10th day of culture) regardless of the initial size of the created spheroids and the drug concentration.
芯片上的细胞系统最近已成为研究新型抗癌药物有效性的有前景的设备。已经报道了几种用于肝癌培养和药物细胞毒性评估的微型设备。然而，关于评估肝癌细胞药物细胞毒性的高通量和简单方法，仍然没有经过验证的报告。本文介绍了抗癌药物（5-氟尿嘧啶，5-FU）对作为肝癌模型的HepG2球体的影响结果。实验基于在微流体系统中的长期三维球体培养，并监测两种选定浓度（0.5 mM和1.0 mM）的5-FU的效果。我们的研究表明，球体的初始大小对药物效果有影响。随着球体直径的增加，耐药性（对于两种测试的5-FU浓度）降低。通过细胞代谢分析以及球体大小的变化都观察到了这种现象。在我们的研究中，我们表明较低的5-FU（0.5 mM）浓度会导致HepG2球体活力的更高下降。此外，由于微系统的构造，无论所创建球体的初始大小和药物浓度如何，我们都观察到了耐药效应（培养第10天）。
