overexpression of the orotate phosphoribosyl-transferase gene enhances the effect of 5-fluorouracil in head and neck squamous cell carcinoma in vitro
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2012
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Abstract
5-Fluorouracil (5-FU) is a widely used drug in head and neck squamous cell carcinoma (HNSCC). In the anabolic pathway of 5-FU, the first step in activation of the drug is phosphorylation of 5-FU by orotate phosphoribosyltransferase (OPRT), which directly metabolizes 5-FU to 5-fluorouridine monophosphate (FUMP) in the presence of 5-phosphoribosyl-1-pyrophosphate. To date, OPRT expression in the tumors has been related to the clinical response or survival of cancer patients receiving 5-FU-based chemotherapy. In this study, we examined whether OPRT expression correlates with the chemosensitivity to 5-FU and cell proliferation in HNSCC. We constitutively expressed an OPRT cDNA in an HNSCC cell line. The effects of OPRT expression on in vitro cell growth and 5-FU cytotoxicity were examined. OPRT transfection increases the cytotoxicity of 5-FU without affecting cell proliferation of HNSCC cells in vitro. These results indicate that OPRT expression plays an important role in the sensitivity of HNSCC to 5-FU chemotherapy.
| Reference Key |
yasumatsu2012journaloverexpression
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|---|---|
| Authors | ;Ryuji Yasumatsu;Torahiko Nakashima;Shizuo Komune |
| Journal | joule |
| Year | 2012 |
| DOI |
10.1155/2012/649605
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| URL | |
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