二甲双胍
厌氧糖酵解
癌症研究
光动力疗法
PI3K/AKT/mTOR通路
糖酵解
癌细胞
葡萄糖摄取
瓦博格效应
内科学
药理学
化学
生物
癌症
医学
细胞凋亡
生物化学
新陈代谢
胰岛素
有机化学
作者
Marta Mascaraque,María Gallego-Rentero,Jimena Nicolás-Morala,Mikel Portillo-Esnaola,José M. Cuezva,Salvador González,Yolanda Gilaberte,Ángeles Juarranz
标识
DOI:10.1016/j.molmet.2022.101496
摘要
Cancer metabolic reprogramming promotes resistance to therapies. In this study, we addressed the role of the Warburg effect in the resistance to photodynamic therapy (PDT) in skin squamous cell carcinoma (sSCC). Furthermore, we assessed the effect of metformin treatment, an antidiabetic type II drug that modulates metabolism, as adjuvant to PDT.For that, we have used two human SCC cell lines: SCC13 and A431, called parental (P) and from these cell lines we have generated the corresponding PDT resistant cells (10GT).Here, we show that 10GT cells induced metabolic reprogramming to an enhanced aerobic glycolysis and reduced activity of oxidative phosphorylation, which could influence the response to PDT. This result was also confirmed in P and 10GT SCC13 tumors developed in mice. The treatment with metformin caused a reduction in aerobic glycolysis and an increase in oxidative phosphorylation in 10GT sSCC cells. Finally, the combination of metformin with PDT improved the cytotoxic effects on P and 10GT cells. The combined treatment induced an increase in the protoporphyrin IX production, in the reactive oxygen species generation and in the AMPK expression and produced the inhibition of AKT/mTOR pathway. The greater efficacy of combined treatments was also seen in vivo, in xenografts of P and 10GT SCC13 cells.Altogether, our results reveal that PDT resistance implies, at least partially, a metabolic reprogramming towards aerobic glycolysis that is prevented by metformin treatment. Therefore, metformin may constitute an excellent adjuvant for PDT in sSCC.
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