| Autor: |
Azambuja JH; Programa de Pós-Graduação Em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Rua Sarmento Leite, 245-Prédio Principal, Porto Alegre, RS, 90050-170, Brazil. julianahazambuja@hotmail.com., Schuh RS; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil., Michels LR; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil., Gelsleichter NE; Programa de Pós-Graduação Em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Rua Sarmento Leite, 245-Prédio Principal, Porto Alegre, RS, 90050-170, Brazil., Beckenkamp LR; Programa de Pós-Graduação Em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Rua Sarmento Leite, 245-Prédio Principal, Porto Alegre, RS, 90050-170, Brazil., Lenz GS; Programa de Pós-Graduação Em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Rua Sarmento Leite, 245-Prédio Principal, Porto Alegre, RS, 90050-170, Brazil., de Oliveira FH; Departamento de Patologia, UFRGS, Porto Alegre, RS, Brazil., Wink MR; Programa de Pós-Graduação Em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Rua Sarmento Leite, 245-Prédio Principal, Porto Alegre, RS, 90050-170, Brazil., Stefani MA; Departamento de Morfologia, UFRGS, Porto Alegre, RS, Brazil., Battastini AMO; Departamento de Bioquímica, UFRGS, Porto Alegre, RS, Brazil., Teixeira HF; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil., Braganhol E; Programa de Pós-Graduação Em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Rua Sarmento Leite, 245-Prédio Principal, Porto Alegre, RS, 90050-170, Brazil. |
| Abstrakt: |
Glioblastoma is the most devastating primary brain tumor and effective therapies are not available. Treatment is based on surgery followed by radio and chemotherapy with temozolomide (TMZ), but TMZ increases patient survival only by 2 months. CD73, an enzyme responsible for adenosine production, emerges as a target for glioblastoma treatment. Indeed, adenosine causes tumor-promoting actions and CD73 inhibition increases sensitivity to TMZ in vitro. Here, a cationic nanoemulsion to nasal delivery of siRNA CD73 (NE-siRNA CD73) aiming glioblastoma treatment was employed alone or in combination with TMZ. In vitro, two glioblastoma cell lines (C6 and U138MG) with a chemo-resistant profile were used. Treatment alone with NE-siRNA CD73 reduced C6 and U138MG glioma cell viability by 70% and 25%, respectively. On the other hand, when NE-siRNA + TMZ combined treatment was employed, a reduction of 85% and 33% of cell viability was observed. Notably, treatment with NE-siRNA CD73 of glioma-bearing Wistar rats reduced tumor size by 80%, 60% more than the standard chemotherapy with TMZ, but no synergistic or additive effect was observed in vivo. Additionally, NE-siRNA CD73, TMZ or combined therapy decreased adenosine levels in liquor confirming the importance of this nucleoside on in vivo GB growth. Finally, no hemolytic potential was observed. These results suggest that nasal administration of NE-siRNA CD73 exhibits higher antiglioma effect when compared to TMZ. However, no synergistic or additive in vivo was promoted by the therapeutic regimen employed in this study. |
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