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| Author(s): |
Janaína Alessandra Silva
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2021-08-31 |
| Examining board members: |
Alison Colquhoun;
Luciana Nogueira de Sousa Andrade;
Carolina Beltrame Del Debbio;
Marimelia Aparecida Porcionatto
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| Advisor: | Alison Colquhoun |
| Abstract | |
Current therapeutic strategies for glioblastoma (GBM) are often ineffective and this is mainly due to increased activity of multidrug-resistant proteins (MRPs) and DNA gene repair such as MGMT. Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and gamma-linolenic acid (GLA) can modulate these mechanisms. Aims. To evaluate the role of polyunsaturated fatty acids (PUFAs) in drug resistance of human GBM cells by checking the effects on tumor growth, incorporation and chemotherapeutic action of Vincristine (VCR) and Temozolomide (TMZ). Methodology. Drug-resistant U87MG-derived cell lines were grown with VCR 0.4 nM and TMZ25 M. Resistant T98G cell lines were produced with VCR 5nM and 112.5 M TMZ. Cell growth assays were performed using DHA, GLA and EPA in U87MG, TMZ resistant (TMZ-R) and VCR(VCR-R) cells. Incorporation, resistance protein activity and ABC transporter gene expression. were evaluated in cells after PUFAs treatments by GCMS assay, Rhodamine 123 and RT-qPCR, respectively. ANOVA with Tukey post test. or t-test were used for statistical analysis to assess statistical significance. Results. In U87MG resistant cells MGMT gene were increased. In U87MG cells, VCR + EPA [100 M] decreased cell number. In VCR-R cells, VCR + EPA [100 M] dimunished cell number. The cells appear to have a decrease in efflux activity after the treatments. The genes ABCB1, ABCC1, ABCC3 and ABCC4 had their expression altered in resistant cells. Conclusion. Each combination between fatty acids and chemotherapy had a very specific characteristic, corroborating with issues found in the literature, but studies on the influence of polyunsaturated fatty acids in GBM are scarce and from the relevance of the data found, it is important for research that more studies are done. (AU) | |
| FAPESP's process: | 15/18311-8 - Influence of polyunsaturated fatty acids in chemotherapy treatments of glioblastoma (GBM) |
| Grantee: | Janaína Alessandra Silva |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |