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Title: Metformin as an adjuvant to photodynamic therapy in resistant basal cell carcinoma cells
Authors: Mascaraque, Marta ORCID SCOPUSID
Delgado-Wicke, Pablo ORCID SCOPUSID
Gracia-Cazaña, Tamara SCOPUSID
González, Salvador SCOPUSID
Gilaberte-Calzada, Yolanda ORCID SCOPUSID
Juarranz, Ángeles ORCID SCOPUSID
Keywords: Carcinoma de células basales; Terapia fotodinámica; Resistencia; Marcadores metabólicos; Metformina
Issue Date: 13-Mar-2020
Publisher: MDPI AG
Citation: Mascaraque, M., Delgado-Wicke, P., Nuevo-Tapioles, C., Gracia-Cazaña, T., Abarca-Lachen, E., González, S., . . . Juarranz, Á. (2020). Metformin as an adjuvant to photodynamic therapy in resistant basal cell carcinoma cells. Cancers, 12(3) doi:10.3390/cancers12030668
Description: Photodynamic Therapy (PDT) with methyl-aminolevulinate (MAL-PDT) is beingused for the treatment of Basal Cell Carcinoma (BCC), although resistant cells may appear.Normal differentiatedcells depend primarily on mitochondrial oxidative phosphorylation (OXPHOS)to generate energy, but cancer cells switch this metabolism to aerobic glycolysis (Warburg effect),influencing the response to therapies. We have analyzed the expression of metabolic markers(β-F1-ATPase/GAPDH (glyceraldehyde-3-phosphate dehydrogenase) ratio, pyruvate kinase M2(PKM2), oxygen consume ratio, and lactate extracellular production) in the resistance to PDT ofmouse BCC cell lines (named ASZ and CSZ, heterozygous forptch1). We have also evaluated theability of metformin (Metf), an antidiabetic type II compound that acts through inhibition of theAMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway to sensitizeresistant cells to PDT. The results obtained indicated that resistant cells showed an aerobic glycolysismetabolism. The treatment with Metf induced arrest in the G0/G1 phase and a reduction in the lactateextracellular production in all cell lines. The addition of Metf to MAL-PDT improved the cytotoxiceffect on parental and resistant cells, which was not dependent on the PS protoporphyrin IX (PpIX)production. After Metf+MAL-PDT treatment, activation of pAMPK was detected, suppressing themTOR pathway in most of the cells. Enhanced PDT-response with Metf was also observed in ASZtumors. In conclusion, Metf increased the response to MAL-PDT in murine BCC cells resistant toPDT with aerobic glycolysis.
ISSN: 2072-6694
Appears in Collections:Artículos de revistas

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