Modelos tumorais 2D e 3D para a avaliação de fármacos

• Autor(a) principal: Barros, Andreia Sofia de Sousa
• Data de Publicação: 2018
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.6/9772
• topic: Cancro do Pâncreas; Culturas Celulares 2d; Doxorrubicina; Esferóides; Resveratrol; Domínio/Área Científica::Ciências Médicas::Ciências Biomédicas

Drug combination emerged as a solution for the treatment of cancer, once this therapeutic approach allows to surpass the drug resistance of cancer cells and, simultaneously, eradicate the tumor. The assessment of drug-combination for pancreatic cancer treatment is usually performed in 2D cell cultures. However, these models are unable to mimic the drug resistance profiles found in pancreatic cancer. Thus, they may overestimate the therapeutic potential of the drug combination, leading to poor therapeutic performance in in vivo assays. Therefore, 3D culture models, especially spheroids, appear as a promising method for screening anticancer drugs, since they are able to mimic the structural and functional features of solid tumors. In the present study, the therapeutic effect and the synergistic potential of a particular combination of drugs in 2D and 3D cell cultures were analyzed and compared for the first time. In this way, the effect of the combination of Doxorubicin:Resveratrol (DOX:RES) (at molar ratios ranging from 5: 1 to 1: 5), in the viability of the pancreatic cancer cell line, PANC-1, was studied. The results showed that the viability of PANC-1 cells was more affected when the DOX:RES combinations contained a higher content of RES (molar ratios of 1:2 to 1:5). These results can be explained, by the ability of RES to reduce the efflux of DOX, mediated by P-glycoprotein (P-gp). Furthermore, these data also revealed that the synergistic effect of the DOX:RES combination was different in both 2D and 3D cell cultures. In fact, although 1:4 and 1:5 DOX: RES ratios were synergistic for these types of cell cultures, their values Combination Index (CI) were lower (more synergistic) in 2D cultures, when compared to spheroids. Overall, the results obtained revealed that the combination DOX:RES is promising approach for the treatment of pancreatic cancer and corroborate the need to perform drug screening.