Long-term interferon-α treatment suppresses tumor growth but promotes metastasis capacity in hepatocellular carcinoma

J Cancer Res Clin Oncol. 2010 Dec;136(12):1891-900. doi: 10.1007/s00432-010-0848-1. Epub 2010 Mar 6.

Abstract

Purpose: To elucidate the effect of IFN-α treatment on tumor growth and metastasis of hepatocellular carcinoma (HCC).

Methods: IFN-α administration was conducted in nude mice using an orthotopic implantation model of human HCC, and the key molecular markers in the IFN-α treatment was detected by immunohistochemistry staining and PCR array.

Results: Up to 12 weeks of IFN-α treatment significantly suppressed tumor growth of HCC, but relatively increased the number of circulating tumor cells, which might be due to the enhanced tumor hypoxia as well as up-regulation of metastasis-related genes, such as HIF-1α, c-met, u-PA, PDGF-A, and IL-8. However, IFN-α had no direct effect on migration and invasion of HCC cells.

Conclusions: IFN-α has janus face of consistently suppressing HCC growth, however, promoting tumor metastasis capacity, which is of clinical indication for the scientific administration of IFN-α and the similar antiangiogenesis drugs for their dual effect on tumor growth and metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / prevention & control*
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Hypoxia
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Immunologic Factors / pharmacology
  • Interferon-alpha / pharmacology*
  • Liver Neoplasms, Experimental / genetics
  • Liver Neoplasms, Experimental / pathology
  • Liver Neoplasms, Experimental / prevention & control*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Metastasis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Analysis
  • Time Factors
  • Tumor Burden / drug effects*
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Immunologic Factors
  • Interferon-alpha
  • Vascular Endothelial Growth Factor A