title: Amprenavir inhibits the migration in human hepatocarcinoma cell and the growth of xenografts.
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.
authors.affiliation: Third Division of Infection Diseases, AORN dei Colli, Naples, Italy. esposvin@libero.it
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Esposito
authors.forename: Alessandra
authors.initials: A
authors.lastname: Verdina
authors.forename: Lucrezia
authors.initials: L
authors.lastname: Manente
authors.forename: Enrico P
authors.initials: EP
authors.lastname: Spugnini
authors.forename: Rosaria
authors.initials: R
authors.lastname: Viglietti
authors.forename: Roberto
authors.initials: R
authors.lastname: Parrella
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pagliano
authors.forename: Giovanni
authors.initials: G
authors.lastname: Parrella
authors.forename: Rossella
authors.initials: R
authors.lastname: Galati
authors.forename: Antonio
authors.initials: A
authors.lastname: De Luca
authors.forename: Alfonso
authors.initials: A
authors.lastname: Baldi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Montesarchio
authors.forename: Antonio
authors.initials: A
authors.lastname: Chirianni
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002219:Carbamates / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005663:Furans; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D013449:Sulfonamides; C095108:amprenavir; D051057:Proto-Oncogene Proteins c-akt; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2