Mechanisms of resistance to chemotherapy in tumors cells.

Author(s)

Clarissa Ribeiro Reily Rocha

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas
• Defense date: 18 dez. 2015

Examining board members

Carlos Frederico Martins Menck; Roger Chammas; Fábio Luís Forti; Oswaldo Keith Okamoto; Bryan Eric Strauss

• Advisor: Carlos Frederico Martins Menck

Abstract

Cancer is one of main cause of death worldwide and the limiting factor is antitumoral therapy resistance. Several mechanisms command drug resistance and fundamental question is how is to unveil the mechanisms involved in it to get a better therapeutic efficacy. We investigated the mechanisms of cisplatin resistance in glioma cells. We demonstrated that cisplatin resistance was p53 independent and DNA repair capacity. It was demonstrated in a in vitro a in vivo model that gluthatione (GSH) is the major resistant factor for cisplatin and temozolomide (TMZ). We observed that the TMZ resistant glioma cell line counted with a high expression of the antioxidant transcription factor NFR2, GCLM and GST. We observed that NFR2 silencing greatly enhanced cell death, high levels of DNA damage upon TMZ treatment. In addition, BSO potentiated TMZ killing in human and murine melanoma using in vitro and in vivo models. Thus, combination of BSO, cisplatin and TMZ is a powerful strategy to optimize tumor killing, thus providing an exciting alternative therapeutic protocol to glioma and melanoma patients. (AU)

• FAPESP's process: 10/20506-8 - Use of gene reporter luciferase to determine DNA repair activity in animals cells
• Grantee: Clarissa Ribeiro Reily Rocha
• Support type: Scholarships in Brazil - Doctorate (Direct)