Sign in to use this feature.

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline

Journals

remove_circle_outline

Article Types

Countries / Regions

Search Results (1)

Search Parameters:
Keywords = afatinib–metformin

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
19 pages, 3133 KB  
Article
Metformin Enhances TKI-Afatinib Cytotoxic Effect, Causing Downregulation of Glycolysis, Epithelial–Mesenchymal Transition, and EGFR-Signaling Pathway Activation in Lung Cancer Cells
by Pedro Barrios-Bernal, Norma Hernandez-Pedro, Mario Orozco-Morales, Rubí Viedma-Rodríguez, José Lucio-Lozada, Federico Avila-Moreno, Andrés F. Cardona, Rafael Rosell and Oscar Arrieta
Pharmaceuticals 2022, 15(3), 381; https://doi.org/10.3390/ph15030381 - 21 Mar 2022
Cited by 13 | Viewed by 4824
Abstract
The combination of metformin and TKIs for non-small cell lung cancer has been proposed as a strategy to overcome resistance of neoplastic cells induced by several molecular mechanisms. This study sought to investigate the effects of a second generation TKI afatinib, metformin, or [...] Read more.
The combination of metformin and TKIs for non-small cell lung cancer has been proposed as a strategy to overcome resistance of neoplastic cells induced by several molecular mechanisms. This study sought to investigate the effects of a second generation TKI afatinib, metformin, or their combination on three adenocarcinoma lung cancer cell lines with different EGFRmutation status. A549, H1975, and HCC827 cell lines were treated with afatinib, metformin, and their combination for 72 h. Afterwards, several parameters were assessed including cytotoxicity, interactions, apoptosis, and EGFR protein levels at the cell membrane and several glycolytic, oxidative phosphorylation (OXPHOS), and EMT expression markers. All cell lines showed additive to synergic interactions for the induction of cytotoxicity caused by the tested combination, as well as an improved pro-apoptotic effect. This effect was accompanied by downregulation of glycolytic, EMT markers, a significant decrease in glucose uptake, extracellular lactate, and a tendency towards increased OXPHOS subunits expression. Interestingly, we observed a better response to the combined therapy in lung cancer cell lines A549 and H1975, which normally have low affinity for TKI treatment. Findings from this study suggest a sensitization to afatinib therapy by metformin in TKI-resistant lung cancer cells, as well as a reduction in cellular glycolytic phenotype. Full article
Show Figures

Figure 1

Back to TopTop