Department of Biochemistry, Molecular Biology and Biotechnology, Faculty of Chemistry, Wroclaw University of Science and Technology, ul. Norwida 4/6, 50-373 Wroclaw, Poland.
Department of Basic Medical Sciences, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211, 50-556 Wroclaw, Poland.
Molecules. 2021 May 27;26(11):3215. doi: 10.3390/molecules26113215.
To study the simultaneous effect of the molecular gradient of polyphenols (curcumin, -resveratrol, and wogonin) and biological factors released from tumor cells on apoptosis of adjacent cells, a novel microfluidic system was designed and manufactured. The small height/volume of microfluidic culture chambers and static conditions allowed for establishing the local microenvironment and maintaining undisturbed concentration profiles of naturally secreted from cells biochemical factors. In all trials, we observe that these conditions significantly affect cell viability by stimulating cell apoptosis at lower concentrations of polyphenols than in traditional multiwell cultures. The observed difference varied between 20.4-87.8% for curcumin, 11.0-37.5% for resveratrol, and 21.7-62.2% for wogonin. At low concentrations of polyphenols, the proapoptotic substances released from adjacent cells, like protein degradation products, significantly influence cell viability. The mean increase in cell mortality was 38.3% for microfluidic cultures. Our research has also confirmed that the gradient microsystem is useful in routine laboratory tests in the same way as a multiwell plate and may be treated as its replacement in the future. We elaborated the new repetitive procedures for cell culture and tests in static gradient conditions, which may become a gold standard of new drug investigations in the future.
为了研究多酚（姜黄素、白藜芦醇和白杨素）的分子梯度与肿瘤细胞释放的生物因子对相邻细胞凋亡的协同作用，设计并制造了一种新型微流控系统。微流控培养室的小高度/体积和静态条件允许建立局部微环境，并保持细胞自然分泌的生化因子的未被干扰的浓度分布。在所有试验中，我们观察到这些条件通过在低于传统多孔培养物的多酚浓度下刺激细胞凋亡，显著影响细胞活力。观察到的差异在姜黄素为 20.4-87.8%、白藜芦醇为 11.0-37.5%和白杨素为 21.7-62.2%之间变化。在多酚的低浓度下，来自相邻细胞的促凋亡物质，如蛋白降解产物，显著影响细胞活力。细胞死亡率的平均增加为 38.3%的微流控培养物。我们的研究还证实，梯度微系统与多孔板一样，可用于常规实验室测试，并且将来可能被视为其替代品。我们详细说明了在静态梯度条件下进行细胞培养和测试的新重复程序，这可能成为未来新药研究的黄金标准。
