Study of metformin effects in mTOR/S6Ks signal transduction pathway in lung cancer cells

• Grant number: 16/02483-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2016
• End date: February 28, 2017
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Principal Investigator: Fernando Moreira Simabuco
• Grantee: Ana Paula Morelli
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Associated research grant: 12/13558-7 - Molecular characterization of S6Ks in obesity and its associated diseases, AP.JP

Abstract

Over the past few years, the mTOR signal transduction pathway has been associated to the control of energy balance of the body, acting either as a sensor of the amount of available nutrients or as a trigger for the expense or storage of energy. The S6Ks proteins have shown an important role in the mTOR signaling, functioning as effectors of this signaling pathway, although still having open questions. Among the diseases related to obesity, as well as to the control or dysfunction of mTOR/S6Ks pathway, one may highlight cancer, whose incidence in obese is clearly higher. Metformin has been used in the treatment of type II diabetes, but many reports in the literature indicate its important role in the fight against cancer (Kasznicki et al, 2014. Wang et al, 2015.). This research project aims to study the effects of metformin treatment on the mTOR/S6Ks signaling transduction pathway in lung cancer cells. For this purpose, A549 lung cancer cells will be subjected to treatment with metformin and a proteomic analysis will be performed from total protein extracts, using the labeling known as SILAC (Stable Isotope Labeling by Amino acids in Cell culture). We expect to find effects in the modulation of several signaling pathways by comparing cells treated with metformin and control cells, including components of the mTOR pathway, such as S6Ks proteins. (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)

MORELLI, ANA PAULA; TORTELLI, THARCISIO CITRANGULO JR JR; BETIM PAVAN, ISADORA CAROLINA; SILVA, FERNANDO RIBACK; GRANATO, DANIELA CAMPOS; PERUCA, GUILHERME FRANCISCO; PAULETTI, BIANCA ALVES; DOMINGUES, ROMENIA RAMOS; NEVES BEZERRA, ROSANGELA MARIA; DE MOURA, LEANDRO PEREIRA; et al. Metformin impairs cisplatin resistance effects in A549 lung cancer cells through mTOR signaling and other metabolic pathways. International Journal of Oncology, v. 58, n. 6, JUN 2021. (16/02483-7, 19/00607-9, 15/22814-5, 17/04269-5, 15/16601-9, 18/14818-9, 16/06457-0, 12/13558-7)