BACKGROUND: 5-Fluorouracil (5-FU) is a widely used drug in head and neck squamous cell carcinoma (HNSCC). Thymidylate synthase (TS), which is the target enzyme of 5-FU, has been demonstrated to be a key regulatory enzyme. In this study, we examined whether TS expression is correlated with chemosensitivity to 5-FU, cell proliferation and clinical outcome in HNSCC. METHODS: An antisense TS cDNA was constitutively expressed in the HNSCC cell line. The effects of TS expression on in vitro cell growth and 5-FU cytotoxicity were examined. We also evaluated the association between TS expression and cell proliferation in surgical specimens, and prognosis in HNSCC patients. RESULTS: Antisense TS transfection increases the cytotoxicity of 5-FU and inhibits cell proliferation in HNSCC cells in vitro. Immunohistochemical expression of TS may have prognostic value in patients with HNSCC. CONCLUSIONS: These results indicate that TS expression plays an important role in the sensitivity of HNSCC to 5-FU chemotherapy. (c) 2008 S. Karger AG, Basel.
BACKGROUND:5-Fluorouracil (5-FU) is a widely used drug in head and neck squamous cell carcinoma (HNSCC). Thymidylate synthase (TS), which is the target enzyme of 5-FU, has been demonstrated to be a key regulatory enzyme. In this study, we examined whether TS expression is correlated with chemosensitivity to 5-FU, cell proliferation and clinical outcome in HNSCC. METHODS: An antisense TS cDNA was constitutively expressed in the HNSCC cell line. The effects of TS expression on in vitro cell growth and 5-FUcytotoxicity were examined. We also evaluated the association between TS expression and cell proliferation in surgical specimens, and prognosis in HNSCC patients. RESULTS: Antisense TS transfection increases the cytotoxicity of 5-FU and inhibits cell proliferation in HNSCC cells in vitro. Immunohistochemical expression of TS may have prognostic value in patients with HNSCC. CONCLUSIONS: These results indicate that TS expression plays an important role in the sensitivity of HNSCC to 5-FU chemotherapy. (c) 2008 S. Karger AG, Basel.