2-Deoxy-D-glucose suppresses the migration and reverses the drug resistance of colon cancer cells through ADAM expression regulation
- Authors
- Park, Ga B.; Chung, Yoon H.; Kim, Daejin
- Issue Date
- Apr-2017
- Publisher
- LIPPINCOTT WILLIAMS & WILKINS
- Keywords
- 2-deoxy-D-glucose; a disintegrin and metalloproteinase; colorectal cancer; drug resistance; epithelial mesenchymal transition
- Citation
- ANTI-CANCER DRUGS, v.28, no.4, pp 410 - 420
- Pages
- 11
- Journal Title
- ANTI-CANCER DRUGS
- Volume
- 28
- Number
- 4
- Start Page
- 410
- End Page
- 420
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/4602
- DOI
- 10.1097/CAD.0000000000000472
- ISSN
- 0959-4973
1473-5741
- Abstract
- 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 drugresistant 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. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
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