Overexpression of the orotate phosphoribosyl-transferase gene enhances the effect of 5-Fluorouracil in head and neck squamous cell carcinoma in vitro.
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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DOI：
10.1155/2012/649605
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发表时间：
2012
影响因子：
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通讯作者：
Komune S
中科院分区：
文献类型：
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作者：
Yasumatsu R;Nakashima T;Komune S
5-氟尿嘧啶（5-FU）是一种广泛应用于头颈部鳞状细胞癌（HNSCC）的药物。在5-FU的合成代谢途径中，药物活化的第一步是通过乳清酸磷酸核糖转移酶（OPRT）磷酸化5-FU，该酶在5-磷酸核糖-1-焦磷酸存在下将5-FU直接代谢为5-氟尿苷单磷酸（FUMP）。迄今为止，肿瘤中的OPRT表达与接受基于5-FU的化疗的癌症患者的临床应答或生存有关。在这项研究中，我们研究了OPRT表达是否与HNSCC对5-FU的化疗敏感性和细胞增殖相关。我们在HNSCC细胞系中组成型表达OPRT cDNA。检测OPRT表达对体外细胞生长和5-FU细胞毒性的影响。OPRT转染增加了5-FU的细胞毒性，而不影响体外HNSCC细胞的细胞增殖。这些结果表明OPRT表达在HNSCC对5-FU化疗的敏感性中起重要作用。
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.