Metformin overcomes metabolic reprogramming-induced resistance of skin squamous cell carcinoma to photodynamic therapy

• DOI: 10.1016/j.molmet.2022.101496
• Publication Date: 2022-04-09T01:31:25Z
• Authors: Marta Mascaraque-...; María Gallego-Ren...; Jimena Nicolás-Mo...; Mikel Portillo-Es...; José M. Cuezva; Salvador González; Yolanda Gilaberte; Ángeles Juarranz
• Keywords: Anaerobic glycolysis; Warburg Effect

Cancer metabolic reprogramming promotes resistance to therapies. In this study, we addressed the role of Warburg effect in photodynamic therapy (PDT) skin squamous cell carcinoma (sSCC). Furthermore, assessed metformin treatment, an antidiabetic type II drug that modulates metabolism, as adjuvant PDT.For that, have used two human SCC lines: SCC13 and A431, called parental (P) from these lines generated corresponding PDT resistant cells (10GT).Here, show 10GT induced enhanced aerobic glycolysis reduced activity oxidative phosphorylation, which could influence response PDT. This result was also confirmed P tumors developed mice. The treatment with caused a reduction increase phosphorylation sSCC cells. Finally, combination improved cytotoxic effects on combined protoporphyrin IX production, reactive oxygen species generation AMPK expression produced inhibition AKT/mTOR pathway. greater efficacy treatments seen vivo, xenografts cells.Altogether, our results reveal implies, at least partially, towards is prevented by treatment. Therefore, may constitute excellent for sSCC.