Characterization of the soluble isoform of FAS protein (CD95) on cisplatin and apoptosis resistance in lung cancer cells using CRISPR technology

• Grant number: 19/25731-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2020
• End date: January 31, 2022
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Principal Investigator: Fernando Moreira Simabuco
• Grantee: Daniel Francisco Guimarães dos Santos Junior
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Associated research grant: 18/14818-9 - Study of molecular targets important for the control of cancer metabolism: the mTOR/S6K pathway as a central role, AP.JP2

Abstract

Lung cancer affects millions of people around the world in recent years and has an extremely aggressive feature, being considered one of the most lethal types of cancer. The FAS protein is an apoptosis signaling protein that has been correlated with chemotherapy resistance in lung cancer. The aim of this study is to develop a specific knockout of soluble FAS protein isoform using CRISPR/Cas9 technology and to evaluate the development of cisplatin chemotherapy resistance in lung cancer cells. A549 lung cancer cells will be used, whether or not treated with cisplatin at a dose that generates drug resistance. Later, cancer-related cellular parameters will be evaluated, such as cell viability, proliferation, and apoptosis-associated cellular pathways through Western blotting. A CRISPR/Cas9 modified A549 cell line not significantly expressing the FAS soluble isoform is expected to be obtained, presenting increased sensitivity to cisplatin chemotherapy treatment. (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)

MANCINI, MARIANA C. S.; MORELLI, ANA P.; SEVERINO, MATHEUS B.; PAVAN, ISADORA C. B.; ZAMBALDE, ERIKA P.; GOIS, MARIANA M.; DA SILVA, LUIZ G. S.; QUINTERO-RUIZ, NATHALIA; ROMEIRO, CAIO F.; DOS SANTOS JR, DANIEL F. G.; et al. Knockout of NRF2 triggers prostate cancer cells death through ROS modulation and sensitizes to cisplatin. Journal of Cellular Biochemistry, v. 123, n. 12, p. 14-pg., 2022-10-03. (20/09310-6, 20/09133-7, 16/06457-0, 20/13660-2, 20/09527-5, 15/00311-1, 20/08684-0, 18/14818-9, 19/00607-9, 19/25582-9, 19/25731-4)