| 2-deoxy-D-glucose increases the efficacy of adriamycin and paclitaxel in human osteosarcoma and non-small cell lung cancers in vivo. | |
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MedLine Citation:
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PMID: 14729604 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Slow-growing cell populations located within solid tumors are difficult to target selectively because most cells in normal tissues also have low replication rates. However, a distinguishing feature between slow-growing normal and tumor cells is the hypoxic microenvironment of the latter, which makes them extraordinarily dependent on anaerobic glycolysis for survival. Previously, we have shown that hypoxic tumor cells exhibit increased sensitivity to inhibitors of glycolysis in three distinct in vitro models. Based on these results, we predicted that combination therapy of a chemotherapeutic agent to target rapidly dividing cells and a glycolytic inhibitor to target slow-growing tumor cells would have better efficacy than either agent alone. Here, we test this strategy in vivo using the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) in combination with Adriamycin (ADR) or paclitaxel in nude mouse xenograft models of human osteosarcoma and non-small cell lung cancer. Nude mice implanted with osteosarcoma cells were divided into four groups as follows: (a) untreated controls; (b) mice treated with ADR alone; (c) mice treated with 2-DG alone; or (d) mice treated with a combination of ADR + 2-DG. Treatment began when tumors were either 50 or 300 mm(3) in volume. Starting with small or large tumors, the ADR + 2-DG combination treatment resulted in significantly slower tumor growth (and therefore longer survival) than the control, 2-DG, or ADR treatments (P < 0.0001). Similar beneficial effects of combination treatment were found with 2-DG and paclitaxel in the MV522 non-small cell lung cancer xenograft model. In summary, the treatment of tumors with both the glycolytic inhibitor 2-DG and ADR or paclitaxel results in a significant reduction in tumor growth compared with either agent alone. Overall, these results, combined with our in vitro data, provide a rationale for initiating clinical trials using glycolytic inhibitors in combination with chemotherapeutic agents to increase their therapeutic effectiveness. |
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Authors:
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Gregory Maschek; Niramol Savaraj; Waldemar Priebe; Paul Braunschweiger; Kara Hamilton; George F Tidmarsh; Linda R De Young; Theodore J Lampidis |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Cancer research Volume: 64 ISSN: 0008-5472 ISO Abbreviation: Cancer Res. Publication Date: 2004 Jan |
Date Detail:
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Created Date: 2004-01-19 Completed Date: 2004-04-01 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 31-4 Citation Subset: IM |
Affiliation:
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Department of Cell Biology and Anatomy, University of Miami, School of Medicine, Miami, Florida 33101, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bone Neoplasms / drug therapy*, pathology Carcinoma, Non-Small-Cell Lung / drug therapy* Deoxyglucose / pharmacology* Doxorubicin / toxicity* Drug Synergism Humans Lung Neoplasms / drug therapy* Mice Mice, Nude Osteosarcoma / drug therapy*, pathology Paclitaxel / toxicity* Transplantation, Heterologous Tumor Cells, Cultured |
| Grant Support | |
ID/Acronym/Agency:
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CA37109/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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154-17-6/Deoxyglucose; 23214-92-8/Doxorubicin; 33069-62-4/Paclitaxel |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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