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Effects of 5'-DFUR and lentinan on cytokines and PyNPase against AH66 ascites hepatoma in rats.

Pyrimidine nucleoside phosphorylase (PyNPase) is an enzyme which converts 5'-deoxy-5-fluorouridine (5'-DFUR) to 5-fluorouracil (5-FU), and is induced by various cytokines in tumor cells. We evaluated a combination of 5'-DFUR and lentinan which is widely used as a biological response modifier (BRM), to verify antitumor effects, the induction of cytokines such as tumor necrosis factor (TNF)-alpha and latent transforming growth factor (TGF)-beta, and PyNPase activity against AH66 ascites hepatoma cells in rats. AH66 ascites hepatoma cells were subcutaneously injected into the backs of Donryu rats. Rats were randomly assigned to a group receiving either 5'-DFUR or lentinan alone, to a group receiving both 5'-DFUR and lentinan, or to a control group. 5'-DFUR was administered orally, and lentinan was administered intraperitoneally. The tumor size, PyNPase activity in the tumor and spleen, and TNF-alpha and TGF-beta in the tumor were examined. The results were as follows. a) Tumor growth was significantly (P < 0.05) inhibited in both the 5'-DFUR group and the 5'-DFUR + Lentinan group when compared to the control group. Tumor growth in the 5'-DFUR + Lentinan group was significantly (P < 0.01) inhibited compared to that in both the 5'-DFUR group and the Lentinan group. b) PyNPase activity in the tumor was significantly (P < 0.01) higher in each group than in the spleen. In the tumor, PyNPase activity was significantly (P < 0.01) higher in the Lentinan group compared to the control group. In the 5'-DFUR + Lentinan group PyNPase activity in the tumor was significantly (P < 0.01) lower compared to the Lentinan group. c) Levels of TNF-alpha and TGF-beta production in the tumor were significantly (P < 0.05) lower in the 5'-DFUR + Lentinan group compared to the control group. These findings suggested that PyNPase activity in the tumor was induced by lentinan but not so in the spleen, and lentinan increased the susceptibility of tumor cells to 5'-DFUR.