Drug resistance evaluation in novel 3D in vitro model

• Published in: Biomedicine & pharmacotherapy 2021-06, Vol.138, p.111536-111536, Article 111536
• Main Authors: Nowacka, Marta, Sterzynska, Karolina, Andrzejewska, Malgorzata, Nowicki, Michal, Januchowski, Radoslaw
• Format: Article
• Language: English
• Subjects: Drug resistance; Ovarian cancer; Spheroids
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2021.111536

Ovarian cancer rates the highest mortality among all gynecological malignancies. The main reason for high mortality is the development of drug resistance. It can be related to changes in the expression of many drug resistance genes as well as expression of extracellular matrix proteins and cell density in the tumor. We developed a simple two-dimensional and three-dimensional model of drug sensitive A2780 and resistant to cisplatin and paclitaxel variants of ovarian cancer cell line. Using MTT assay, we compared drug resistance in two-dimensional and three-dimensional cell culture conditions. Real-time polymerase chain reaction analysis was used to compare the expression of drug resistance genes. The expression of proteins in spheroids was determined by immunohistochemistry. We observed a moderate increase in cisplatin resistance and a significant increase in paclitaxel resistance between two-dimensional and three-dimensional cell culture conditions. Our findings show that changes in the expression of drug resistance genes may play a crucial role in the drug resistance of cancer cells in traditional cell culture. On the other hand, the drug resistance in spheroids may result from different mechanisms such as cell density in the spheroid, extracellular matrix proteins expression and drug capacity to diffuse into the spheroid. [Display omitted] •Resistance to cisplatin and paclitaxel in two-dimensional and three-dimensional cell culture conditions was examined.•In two-dimensional cell culture, changes in the genes expression might be the pivotal mechanism leading to drug resistance.•In three-dimensional cell culture, tissue-specific mechanisms might be crucial in drug resistance development.