S-1, an oral fluoropyrimidine anti-cancer agent, enhanced radiosensitivity in a human oral cancer cell line in vivo and in vitro: involvement possibility of inhibition of survival signal, Akt/PKB.

To examine the effect of an oral fluoropyrimidine anti-cancer agent (S-1) on the radiosensitivity of a human oral cancer cell line with focusing on inhibition of survival signal, Akt/PKB. A human oral cell cancer cell line B88 was used. Activation of Akt/PKB in vivo was examined by immunohistochemistry, and apoptotic cells were detected by TUNEL method. Activation of Akt/PKB in vitro was investigated by Western blot and ELISA, and apoptotic cells were detected by Hoechst 33258 staining. S-1 (10 mg/kg/day or 50 microg/ml) greatly enhanced radiosensitivity in B88 cells by suppressing the activation of Akt/PKB. Significant increase in the percentage of apoptotic cells was observed in S-1 treated B88 cells. Survival signals Akt/PKB may be involved in determining radiosensitivity. S-1, an oral fluoropyrimidine anti-cancer agent can exert the enhancing effect on radiation by suppressing the activation of Akt/PKB.