RESUMO
Cancer cell resistance to chemotherapy is associated with a poor prognosis. The compound 2-deoxy-D-glucose (2-DG) enhances the effect of chemotherapy against cancer cells lines in vitro and in vivo. However, its effect on the epithelial to mesenchymal transition (EMT) in drug-resistant cancer cells has not been fully elucidated. In this study, we investigated whether treatment of 5-fluorouracil or oxaliplatin-resistant colorectal cancer (CRC) cells with 2-DG suppressed their migratory activity and enhanced their susceptibility to chemotherapy. Chemoresistant CRC cells stably expressed drug resistance-related proteins (MDR1, MRP1, MRP2, and MRP3) and showed mesenchymal characteristics and a migratory phenotype. 2-DG treatment attenuated glycolysis-related enzyme expression, invasion activity, and EMT-related cytokine secretion in drug-resistant CRC cells. In addition, 2-DG inhibited the activation of a disintegrin and metalloproteinase 10 (ADAM10) and ADAM17. Gene silencing of ADAM10 and ADAM17 with small interfering RNA downregulated mesenchymal properties, reduced EMT-associated cytokine secretion, and rendered chemoresistant cells susceptible to anticancer drug treatment. Collectively, these findings suggest that increased glycolytic metabolism in drug-resistant cells has an effect on both migratory activity and cell viability through the activation of ADAM10 and ADAM17.
Assuntos
Proteína ADAM10/biossíntese , Proteína ADAM17/biossíntese , Secretases da Proteína Precursora do Amiloide/biossíntese , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/enzimologia , Desoxiglucose/farmacologia , Proteínas de Membrana/biossíntese , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Neoplasias do Colo/patologia , Resistencia a Medicamentos Antineoplásicos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Glicólise , Células HCT116 , Células HT29 , HumanosRESUMO
We have investigated whether extremely low frequency magnetic field (ELF-MF) induces lipid peroxidation and reactive oxygen species in mouse cerebellum. After exposure to 60 Hz ELF-MF at 2.3 mT intensity for 3 hours, there was a significant increase in malondialdehyde level and hydroxyl radical. ELF-MF significantly induced concomitant increase in superoxide dismutase without alteration in glutathione peroxidase activity. While glutathione contents were not altered, ascorbic acid levels were significantly decreased by ELF-MF exposure. These results indicate that ELF-MF may induce oxidative stress in mouse cerebellum. However, the mechanism remains further to be characterized.
