Role of GCHI in temozolomide resistance through no production and Nrf2 activation in glioblastoma multiforme

• Grant number: 18/12238-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2019
• End date: January 31, 2021
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Fabiana Henriques Machado de Melo
• Grantee: Bruno Macedo Pinto
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

1143/5000Glioblastoma multiforme is considered the primary tumor of the central nervous system of higher incidence in the population, besides being an extremely aggressive cancer with high mortality rate. Although there have been several advances in diagnosis and therapy, the prognosis of patients with glioblastoma multiforme remains very poor due to the difficulty of accurately predicting sensitivity or resistance to chemotherapy, difficulty in surgical access, high recurrence rate, high lethality and low survival. One of the mechanisms associated with migration, proliferation and angiogenesis in glioblastoma multiforme is the increase of nitric oxide produced by the nitric oxide synthase enzyme, which may also be associated with the mechanism of resistance to the increase of reactive oxygen species caused by the use of temozolomide, through of the activation of the transcription factor NRF2. Based on this information, the objective of this study is to evaluate if the increase of GCH1 enzyme expression in response to NRF2 with a consequent increase in nitric oxide is associated with the mechanism of resistance to temozolomide in glioblastoma cells.