The influence of tumor metabolism on tumor progression and drug resistance

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The influence of tumor metabolism on tumor progression and drug resistance

Friday, 15.02.2019


Diana Tavares-Valente1,2; Sara Granja1; Fátima Baltazar1; Odília Queirós2

1 Life and Health Sciences Research Institute (ICVS)/ School of Medicine/ University of Minho, Campus de Gualtar, Braga, 4710-057, Portugal;

2 IINFACTS - Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, University Institute of Health Sciences (IUCS), CESPU, CRL, Gandra, Portugal


Gliomas are characterized by a marked glycolytic metabolism with a consequent production of massive amounts of lactate, even in the presence of normal levels of oxygen, associated to increased invasion capacity and to higher resistance to conventional treatment. This work aimed to understand how the metabolic modulation can influence tumour aggressive features and its potential to be used as complementary therapy. We assessed the effect of bioenergetic modulators (BMs) targeting different metabolic pathways in glioma cell characteristics. The in vivo effect of BMs was evaluated using the chicken chorioallantoic membrane model. Additionally, the effect of pre‐treatment with BMs in the response to the antitumour drug temozolomide (TMZ) was analysed in vitro. Cell treatment with the BMs induced a decrease in cell viability and in migratory/invasion abilities, as well as modifications in metabolic parameters (glucose, lactate and ATP) and increased the cytotoxicity of the conventional drug TMZ. Furthermore, all BMs decreased the tumour growth and the number of blood vessels in an in vivo model. Our results demonstrate that metabolic modulation has the potential to be used as therapy to decrease the aggressiveness of the tumours or to be combined with conventional drugs used in glioma treatment.


Journal of Cellular and Molecular Medicine

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050502/