Inhibition of monocarboxylate transporter-1 (MCT1) by AZD3965 enhances radiosensitivity by reducing lactate transport
| Autor: | Brian A. Telfer, Kaye J. Williams, Kathryn G. Blount, Susan E. Critchlow, Ian J. Stratford, Amy L. Chadwick, Paul D. Smith, Becky Bola, Filippos Michopoulos |
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| Rok vydání: | 2014 |
| Předmět: |
Lactate transport
Monocarboxylic Acid Transporters Cancer Research Pyrimidinones Thiophenes Radiation Tolerance Article In vivo Cell Line Tumor Neoplasms Animals Cluster Analysis Humans Metabolomics Glycolysis Enzyme kinetics Radiosensitivity Monocarboxylate transporter biology Symporters Biological Transport Xenograft Model Antitumor Assays Tumor Burden Disease Models Animal Oxidative Stress Monocarboxylate transporter 1 Oncology Biochemistry Cell culture biology.protein Cancer research Lactates Female sense organs |
| Zdroj: | Molecular cancer therapeutics. 13(12) |
| ISSN: | 1538-8514 |
| Popis: | Inhibition of the monocarboxylate transporter MCT1 by AZD3965 results in an increase in glycolysis in human tumor cell lines and xenografts. This is indicated by changes in the levels of specific glycolytic metabolites and in changes in glycolytic enzyme kinetics. These drug-induced metabolic changes translate into an inhibition of tumor growth in vivo. Thus, we combined AZD3965 with fractionated radiation to treat small cell lung cancer (SCLC) xenografts and showed that the combination provided a significantly greater therapeutic effect than the use of either modality alone. These results strongly support the notion of combining MCT1 inhibition with radiotherapy in the treatment of SCLC and other solid tumors. Mol Cancer Ther; 13(12); 2805–16. ©2014 AACR. |
| Databáze: | OpenAIRE |
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