Interferon-alpha 2a up-regulated thymidine phosphorylase and enhanced antitumor effect of capecitabine on hepatocellular carcinoma in nude mice.

Purpose. To investigate the antitumor effect of interferon-alpha 2a (IFN-α2a) combined with capecitabine on hepatocellular carcinoma (HCC) in nude mice in relation to thymidine phosphorylase (TP) expression. Methods. Thirty nude mice bearing orthotopic xenografts of a human HCC tumor (LCI-D20) were divided into control, capecitabine, IFN-α2a, and combination (capecitabine plus IFN-α2a) groups. Tumor growth was determined by measuring the tumor volume. An enzyme-linked immunosorbent assay (ELISA) was used to study the TP expression in the cancer tissues of the liver. Results. IFN-α2a enhanced the sensitivity of the LCI-D20 tumor response to capecitabine treatment. The tumor volume was significantly reduced in the capecitabine (455±236 mm³), IFN-α2a (248±114 mm³) or combination (46±29 mm³) treatment groups as compared to the control (1,033±146 mm³) (P<0.01). A significant difference was also found between the single treatment (capecitabine or interferon) and combination treatment group (P<0.01 and P<0.05, respectively). IFN-α2a up-regulated TP expression in LCI-D20 tumor. An approximate 1.5-fold increase in TP expression was observed in the mice which received IFN-α2a treatment compared to the control mice. Conclusion. IFN-α2a enhanced the antitumor effect of capecitabine on HCC in nude mice, which might be ascribed to the up-regulation of TP expression in liver cancer tissues by IFN-α2a. [ABSTRACT FROM AUTHOR]