| Hypoxia induces resistance to 5-fluorouracil in oral cancer cells via G(1) phase cell cycle arrest. | |
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MedLine Citation:
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PMID: 18710819 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Malignant tumors are exposed to various levels of hypoxic condition in vivo. It has been known that tumor cells under hypoxia are resistant to chemotherapies. To clarify the mechanism of the hypoxia-induced chemoresistance, we evaluated the effects of hypoxia on the resistance of oral squamous cell carcinoma (OSCC) cell lines to 5-fluorouracil (5-FU). OSCC cells were divided to two groups by the proliferation activity under hypoxic condition; hypoxia-resistant (HR) and hypoxia-sensitive (HS) cells. Growth of HS cells were inhibited by hypoxia and introduced to G(1) arrest in cell cycle. 5-FU effect on HS cell viability was markedly reduced in hypoxic condition without an induction of chemoresistant related protein, P-glycoprotein. However, proliferation, cell cycle, and 5-FU sensitivity of HR cells were not affected by hypoxia. Hypoxia-inducible factor (HIF)-1alpha was induced by hypoxia in all OSCC cell lines, but diminished in HS cells within 48h. Expression of p21 and p27 was strongly augmented and CyclinD expression was reduced by hypoxia in HS cells. However, the expression of these proteins was constitutive in HR cells during 48h hypoxic culture. Phosphorylation of mammalian target of rapamycin (mTOR) was reduced by hypoxia in HS cells. From these findings, we concluded that HS OSCC cells acquire 5-FU resistance under hypoxia by G(1)/S transition through an upregulation of cell cycle inhibitors. |
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Authors:
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Sayaka Yoshiba; Daisuke Ito; Tatsuhito Nagumo; Tatsuo Shirota; Masashi Hatori; Satoru Shintani |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-08-16 |
Journal Detail:
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Title: Oral oncology Volume: 45 ISSN: 1368-8375 ISO Abbreviation: Oral Oncol. Publication Date: 2009 Feb |
Date Detail:
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Created Date: 2009-01-28 Completed Date: 2009-11-23 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9709118 Medline TA: Oral Oncol Country: England |
Other Details:
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Languages: eng Pagination: 109-15 Citation Subset: IM |
Affiliation:
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Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, Kitasenzoku 2-1-1, Ohta-ku, Tokyo 145-8515, Japan. yoshiba@senzoku.showa-u.ac.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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pharmacology* Blotting, Western Carcinoma, Squamous Cell / drug therapy*, metabolism Cell Cycle / drug effects, physiology Cell Hypoxia / physiology* Cell Line, Tumor / drug effects, metabolism Cell Proliferation / drug effects Cyclin D / metabolism Drug Resistance, Neoplasm / physiology* Fluorouracil / pharmacology* G1 Phase / drug effects, physiology Humans Mouth Neoplasms / drug therapy*, metabolism Transcription Factors / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Cyclin D; 0/Transcription Factors; 51-21-8/Fluorouracil |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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