Chemotherapy has shown little antitumor activity against advanced
oral squamous cell carcinoma (OSCC) patients. Therefore, there is an urgent need to develop more effective therapeutic methods for patients with advanced OSCC.
Lentinan, beta-(1-->3)-
D-glucan, an extract from the edible mushroom, Lentinus edodes, has been reported to show direct antitumor effects and various immunomodulatory effects. S-1 is an oral
antineoplastic agent that can induce apoptosis in various types of
cancer cells, including OSCC. Hence, combined treatment of
cancer cells with
Lentinan and S-1 might exert dramatic antitumor effects on OSCC cells. In this study, the response of human OSCC cells to
Lentinan alone and in combination with S-1 was examined using nude mouse xenograft models. S-1 (6.9 mg/kg/day, 7 times/week) was administered orally and
Lentinan (0.1 mg/kg/day, 2 times/week) was injected into peritumoral tissue for three weeks. Apoptotic cells were detected by a TUNEL method. The gene expression level of
thymidylate synthase (TS),
dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyl
transferase (OPRT) was determined using microdissection and RT-PCR, and their
protein levels were determined using ELISA. Combined
therapy of
Lentinan and S-1 markedly exerted antitumor effects on human OSCC xenografts and significantly induced apoptotic cells in
tumors treated with
Lentinan plus S-1. Microdissection and RT-PCR revealed that the expression of TS and DPD
mRNA was down-regulated and that expression of OPRT
mRNA was up-regulated in
tumors administered the combined treatment. Moreover, ELISA indicated that the
protein levels of TS and DPD were down-regulated, and that OPRT was up-regulated in
tumors treated with the combined
therapy. During the experimental period, no loss of
body weight was observed in mice treated with the combined
therapy. These findings demonstrate that the combination of
Lentinan and S-1 is effective against OSCC and has the potential of being a new therapeutic tool for future treatment of these
tumors.