Amprenavir inhibits the migration in human hepatocarcinoma cell and the growth of xenografts

Vincenzo Esposito, Alessandra Verdina, Lucrezia Manente, Enrico P. Spugnini, Rosaria Viglietti, Roberto Parrella, Pasquale Pagliano, Giovanni Parrella, Rossella Galati, Antonio De Luca, Alfonso Baldi, Vincenzo Montesarchio, Antonio Chirianni

Research output: Contribution to journalArticlepeer-review

Abstract

The introduction of HAART (highly-active-antiretroviral-therapy) has resulted in extended survival of HIV positive patients. Conversely, due to the prolonged expectancy of life and the ageing of the HIV positive population, tumors are now one of the major cause of death, and among them hepatocellular carcinoma (HCC) has become a growing concern in these patients. Considering the potential anti-tumoral effects of HIV protease inhibitors, we decided to evaluate the anti-tumoral activity of Amprenavir on liver carcinoma and to evaluate its potential synergistic effects in combination with standard chemoterapic drugs, such as Doxorubicin. Our results indicate that Amprenavir had direct inhibitory effects on invasion of Huh-7 hepatocarcinoma cell lines, inhibiting MMP proteolytic activation. Amprenavir was able to delay the growth of hepatocarcinoma xenografts in nude mice and had a synergistic effect with Doxorubicin. Furthermore, Amprenavir was able to promote regression of hepatocarcinoma growth in vivo by anti-angiogenetic and overall anti-tumor activities, independently by PI3K/AKT related pathways that at today is one of the more suggestive hypothesis to explain the anti-tumor effects of the different protease inhibitors. In summary these findings suggest novel anti-neoplastic action of Amprenavir on liver cancer showing the possibility of novel combination therapies.

Original languageEnglish
Pages (from-to)640-645
Number of pages6
JournalJournal of Cellular Physiology
Volume228
Issue number3
DOIs
Publication statusPublished - Mar 2013

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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