Influence on 5-fluorouracil metabolism by combination of interferon-alpha and 5-fluorouracil against human hepatocellular carcinoma xenografts

摘要

To investigate the effect of biochemical modulation on antitumor activity shown by the combination of 5-Fluorouracil (5-FU) and interferon-alpha (IFN-alpha), experimental therapy was performed on human hepatocellular carcinoma cell (HuH7, PLC/PLF/5) xenografts inoculated into nude mice, using 5-FU and IFN-alpha, either alone or in combination. These agents showed antitumor activity in different degrees. Although IFN-alpha, given as 100,000 units/mouse/3 times/week subcutaneously x 6, and 5-FU, given as 0.5 mg/mouse/3 times/week intraperitoneally, showed addititive antitumor effect against HuH7 and PLC/PLF/5, the activities of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), orotate phosphoribosyltransferase (OPRT), uridine phosphorylase (UP) and uridine kinase (UK) were not significantly influenced in the tumors treated with the 5-FU/IFN-alpha combination, compared with those treated with 5-FU or IFN-alpha alone. This suggested that antitumor activity of 5-FU and IFN-alpha in combination was not significantly involved in 5-FU metabolism in two human hepatocellular carcinoma cell lines examined.