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

J Cancer Res Clin Oncol. 2004 Sep;130(9):546-50. doi: 10.1007/s00432-004-0565-8. Epub 2004 Apr 8.

Abstract

Purpose: To investigate the antitumor effect of interferon-alpha 2a (IFN-alpha2a) 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-alpha2a, and combination (capecitabine plus IFN-alpha2a) 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-alpha2a enhanced the sensitivity of the LCI-D20 tumor response to capecitabine treatment. The tumor volume was significantly reduced in the capecitabine (455+/-236 mm(3)), IFN-alpha2a (248 +/- 114 mm(3)) or combination (46 +/- 29 mm(3)) treatment groups as compared to the control (1,033 +/- 146 mm(3)) (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-alpha2a 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-alpha2a treatment compared to the control mice.

Conclusion: IFN-alpha2a 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-alpha2a.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / pharmacology*
  • Capecitabine
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / enzymology
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacology*
  • Enzyme-Linked Immunosorbent Assay
  • Fluorouracil / analogs & derivatives
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Interferon-alpha / pharmacology*
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / enzymology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Thymidine Phosphorylase / drug effects*
  • Transplantation, Heterologous
  • Up-Regulation / drug effects

Substances

  • Antimetabolites, Antineoplastic
  • Interferon-alpha
  • Deoxycytidine
  • Capecitabine
  • Thymidine Phosphorylase
  • Fluorouracil