Lipid metabolism and multiple drug resistance in brain tumours

• Grant number: 22/07090-4
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2022
• End date: February 28, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Alison Colquhoun
• Grantee: Alison Colquhoun
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Gliomas are known for their poor prognosis and tendency to develop resistance to chemotherapies currently available in the clinic. There is evidence of the ability of polyunsaturated fatty acids (PUFAs) of the n-3 family, eicosapentaenoic acid (20:5 n-3) (EPA) and docosahexaenoic acid (22:6 n-3) (DHA), to interfere with resistance to chemotherapy in various tumours. PUFAs can influence aspects of cell proliferation and death in addition to interfering with migration and invasion processes, but the effects and mechanisms of action of these PUFAs on resistance to chemotherapy are less well known in gliomas. The project aims to better understand how n-3 PUFAs interfere in the biology of gliomas by studying the effect of n-3 PUFAs on chemotherapy resistance in chemotherapy-sensitive and chemotherapy-resistant glioma cells in vitro and in vivo. In addition, we intend to combine the effects of n-3 PUFAs with other compounds capable of disrupting lipid metabolism in search of even more pronounced effects than those observed individually. The project will focus on the effects of treatments on the cell cycle; apoptosis; ferroptosis; cell migration and invasion; energy, fatty acid, and eicosanoid metabolism; and resistance to chemotherapy. It is hoped that this approach will provide a better understanding of the action of n-3 PUFAs on glioma cells both in vitro and in vivo and identify whether they have the potential to improve cellular response to chemotherapy. In parallel, the protein expression of 15HPGD and PTGR1 will be evaluated by immunohistochemistry as a possible prognostic marker for use in SUS pathology laboratories, together with markers already used in current clinical practice. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SILVA, JANAINA ALESSANDRA; COLQUHOUN, ALISON. Effect of Polyunsaturated Fatty Acids on Temozolomide Drug-Sensitive and Drug-Resistant Glioblastoma Cells. BIOMEDICINES, v. 11, n. 3, p. 21-pg., 2023-03-01. (18/15646-7, 22/07090-4, 15/18311-8)