期刊
INTERNATIONAL JOURNAL OF CANCER
卷 127, 期 10, 页码 2478-2485出版社
WILEY
DOI: 10.1002/ijc.25431
关键词
metastasis; metabolic therapy; calorie restriction; VM mice; DON
类别
资金
- NIH [NS-055195, CA-102135]
- Boston College
Metastatic cancer is a major cause of morbidity and mortality. Current therapeutic options consist of chemotherapy, radiation or targeted therapies. However, these therapies are often toxic, effective over a small range of cancer types or result in drug resistance. Therefore, a more global, less toxic strategy for the management of metastatic cancer is required. Although most cancers display increased glucose metabolism, glutamine is also a major energy substrate for many cancers. We evaluated the antimetastatic potential of 6-diazo-5-oxo-L-norleucine (DON), a glutamine analog, using the new VM mouse model of systemic metastasis. We found that primary tumor growth was similar to 20-fold less in DON-treated mice than in untreated control mice. We also found that DON treatment inhibited metastasis to liver, lung and kidney as detected by bioluminescence imaging and histology. Our findings provide proof of concept that metabolic therapies targeting glutamine metabolism can manage systemic metastatic cancer.
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