Department of Histology and Embryology, Poznan University of Medical Sciences, PL-61-781 Poznan, Poland.
Institute of Health Sciences, Collegium Medicum, University of Zielona Gora, Zyty 28 St, 65-046 Zielona Gora, Poland.
Biomed Pharmacother. 2021 Jun;138:111536. doi: 10.1016/j.biopha.2021.111536. Epub 2021 Mar 31.
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.
卵巢癌是妇科恶性肿瘤中死亡率最高的。高死亡率的主要原因是耐药性的发展。这可能与许多耐药基因的表达变化以及肿瘤中外细胞基质蛋白和细胞密度的表达有关。我们建立了简单的二维和三维顺铂和紫杉醇耐药卵巢癌细胞系药物敏感 A2780 变异体的模型。我们使用 MTT 检测比较了二维和三维细胞培养条件下的耐药性。实时聚合酶链反应分析用于比较耐药基因的表达。通过免疫组织化学测定球体中蛋白质的表达。我们观察到，在二维和三维细胞培养条件下，顺铂耐药性中度增加，紫杉醇耐药性显著增加。我们的研究结果表明，耐药基因表达的变化可能在传统细胞培养中癌细胞耐药性中起关键作用。另一方面，球体中的耐药性可能源于不同的机制，例如球体中的细胞密度、细胞外基质蛋白的表达以及药物扩散到球体中的能力。
