Metformin treatment response is dependent on glucose growth conditions and metabolic phenotype in colorectal cancer cells
Autor: | Gro V. Røsland, Kjetil Søreide, Tia R. Tidwell, Ansooya Avinash Bokil, Abdelnour H. Alhourani, Karl Johan Tronstad, Hanne R. Hagland |
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Rok vydání: | 2021 |
Předmět: |
kolorektal kreft
endocrine system diseases Colorectal cancer Science Type 2 diabetes Pharmacology Article Medicine Glycolysis Cancer Multidisciplinary Cancer prevention biology business.industry Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762 [VDP] nutritional and metabolic diseases medicine.disease Cancer metabolism Metformin Cancer cell biology.protein GLUT1 metformin tarmkreft business medicine.drug |
Zdroj: | Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-10 (2021) |
ISSN: | 2045-2322 |
Popis: | Cancer cells exhibit altered metabolism, a phenomenon described a century ago by Otto Warburg. However, metabolic drug targeting is considered an underutilized and poorly understood area of cancer therapy. Metformin, a metabolic drug commonly used to treat type 2 diabetes, has been associated with lower cancer incidence, although studies are inconclusive concerning effectiveness of the drug in treatment or cancer prevention. The aim of this study was to determine how glucose concentration influences cancer cells’ response to metformin, highlighting why metformin studies are inconsistent. We used two colorectal cancer cell lines with different growth rates and clinically achievable metformin concentrations. We found that fast growing SW948 are more glycolytic in terms of metabolism, while the slower growing SW1116 are reliant on mitochondrial respiration. Both cell lines show inhibitory growth after metformin treatment under physiological glucose conditions, but not in high glucose conditions. Furthermore, SW1116 converges with SW948 at a more glycolytic phenotype after metformin treatment. This metabolic shift is supported by changed GLUT1 expression. Thus, cells having different metabolic phenotypes, show a clear differential response to metformin treatment based on glucose concentration. This demonstrates the importance of growth conditions for experiments or clinical studies involving metabolic drugs such as metformin. |
Databáze: | OpenAIRE |
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