Characterization of lung cancer cell lines for resistance to cisplatin

• Grant number: 15/15184-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2015
• End date: July 31, 2017
• Field of knowledge: Biological Sciences - Genetics - Mutagenesis
• Principal Investigator: Carlos Frederico Martins Menck
• Grantee: Matheus Molina Silva
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 14/15982-6 - Consequences of repair deficiencies in damaged genome, AP.TEM
• Associated scholarship(s): 16/23100-9 - The influence of the circadian cycle in resistance to cisplatin in cancer cells, BE.EP.IC

Abstract

Cancer is one of the most important causes of deaths in Brazil and worldwide, with lung cancer being the most deadly and invasive type, with more than one million cases diagnosed every year. The high rate of mortality is mainly due to the lack of treatments that provide permanent cure or even guarantee the patient a longer survival rate. The preferred procedure is surgical resection, which is not always an option due to the location of the tumor and the condition of the patient. That leaves as an alternative the chemotherapy treatment, in most cases based on the cytotoxicity caused by the induction of DNA damage of tumor cells by therapeutic agents. However, changes in the protection systems of the genome may arise, causing resistance to chemotherapy and consequently reducing the success of the treatment. Among these changes, the increased expression of XPF and ERCC1 proteins in tumor cells stand out, these proteins being components of the nucleotide excision repair pathway (NER). Thus, this project aims to characterize four lines of lung cancer cells by their sensitivity to cisplatin, a chemotherapeutic widely used clinically, and to understand the relation between the referred sensitivity, the mRNA and proteins expression levels of XPF and ERCC1, and the repair of the caused injuries. This project will provide the basis for potential interference studies in the activity of these genes, enhancing the action of cisplatin.

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, MATHEUS MOLINA; REILY ROCHA, CLARISSA RIBEIRO; KINKER, GABRIELA SARTI; PELEGRINI, ALESSANDRA LUIZA; MARTINS MENCK, CARLOS FREDERICO. The balance between NRF2/GSH antioxidant mediated pathway and DNA repair modulates cisplatin resistance in lung cancer cells. SCIENTIFIC REPORTS, v. 9, NOV 27 2019. (14/15982-6, 15/15184-5, 13/08028-1, 17/24217-0)