Overexpression of the Orotate Phosphoribosyl-Transferase Gene Enhances the Effect of 5-Fluorouracil in Head and Neck Squamous Cell Carcinoma In Vitro

Abstract EN

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.