Dataset Information

Metformin impairs cisplatin effects in cell size and proliferation of A549 lung cancer cells, modulating the mTOR and other metabolic pathways.

ABSTRACT: Lung cancer is the leading cause of cancer death worldwide and reports innate and acquired therapeutic resistance to cisplatin. Metformin (MET), an antidiabetic agent with potential antitumor activity, overcomes cisplatin resistance in some cancers through AMPK-dependent and independent mechanisms. MET is a potential treatment in cells with LKB1 mutation, even with the impairment of AMPK and overactivation of mTOR signaling. The present study investigated the role of mTOR signaling and other signaling pathways after MET treatment in control and resistant A549 cells, mapping pathways and possible targets for cisplatin sensitivity induced by metformin.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

DISEASE(S): Lung Cancer

SUBMITTER: Adriana Franco Paes Leme

LAB HEAD: Adriana Franco Paes Leme

PROVIDER: PXD017645 | Pride | 2021-09-09

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	24ago_FernandoSimabuco_C_MET_1_1.raw	Raw
	24ago_FernandoSimabuco_C_MET_1_10.raw	Raw
	24ago_FernandoSimabuco_C_MET_1_2.raw	Raw
	24ago_FernandoSimabuco_C_MET_1_3.raw	Raw
	24ago_FernandoSimabuco_C_MET_1_4.raw	Raw

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Metformin impairs cisplatin resistance effects in A549 lung cancer cells through mTOR signaling and other metabolic pathways.

Morelli Ana Paula AP Tortelli Tharcísio Citrângulo TC Pavan Isadora Carolina Betim ICB Silva Fernando Riback FR Granato Daniela Campos DC Peruca Guilherme Francisco GF Pauletti Bianca Alves BA Domingues Romênia Ramos RR Bezerra Rosangela Maria Neves RMN De Moura Leandro Pereira LP Paes Leme Adriana Franco AF Chammas Roger R Simabuco Fernando Moreira FM

International journal of oncology 20210413 6

Lung cancer is the leading cause of cancer‑associated death worldwide and exhibits intrinsic and acquired therapeutic resistance to cisplatin (CIS). The present study investigated the role of mTOR signaling and other signaling pathways after metformin (MET) treatment in control and cisplatin‑resistant A549 cells, mapping pathways and possible targets involved in CIS sensitivity. MTT, flow cytometry, clonogenic assay, western blotting, proteomic analysis using the Stable Isotope Labeling by Amino ...[more]

PMID: 33846781

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Project description:Epidemiological studies and cardiovascular prevention trials have shown that low-dose aspirin (ASA) can inhibit colorectal cancer (CRC) incidence and mortality, including inhibition of distant metastases. Metformin (MET) has also been associated with decreased CRC incidence and mortality in meta-analyses of epidemiological studies in diabetics and has been shown to decrease by 40% colorectal adenoma recurrence in a randomized trial. Recent studies have shown that ASA is an inhibitor of mTOR/S6K1 and an activator of AMPK, targeting regulators of intracellular energy homeostasis and metabolism, and that the combination of ASA and MET, another AMPK activator and S6K1 inhibitor, has a striking additive effect on AMPK activation and mTOR inhibition, with increased autophagy and decreased cell growth in CRC cell lines. While both drugs are being tested as single agents, their combination has not been tested in trials. This is a randomized, placebo-controlled, double blind, 2x2 biomarker trial of ASA and MET to test the activity of either agent alone and the potential synergism of their combination on a set of surrogate biomarkers of colorectal carcinogenesis. After surgery 160 patients with stage I-III colon cancer will randomly be assigned in a four-arm trial to either ASA, 100 mg day, MET 850 mg bid, their combination, or placebo for one year. The primary endpoint biomarker is the change, defined as the difference between pre- and post-treatment expression of nuclear factor kappa-B (NFκB), in the unaffected mucosa of proximal and distal colon obtained by multiple biopsies in two paired colonoscopies one year apart. Additional biomarkers will include: 1) the genomic profile of candidate genes, pathways, and overall genomic patterns in tissue biopsies by genome wide gene expression arrays; 2) the IHC expression of tissue pS6K, p53, beta-catenin, PI3K; 3) the associations of mutations and SNPs with treatment response by next generation sequencing of primary tumors; 4) the measurement of circulating IL-6, CRP and VEGF and 5) plasma and colonic MET concentrations and their correlation with biomarker profiles.