Evaluation of antitumoral properties of the protease inhibitor indinavir in a murine model of hepatocarcinoma

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Vincenzo EspositoAntonio Chirianni

Abstract

Accumulating evidences show a higher incidence of hepatic neoplasm in HIV/hepatitis C virus (HCV)-coinfected individuals compared with HCV-monoinfected patients. Treatment with HIV-1 protease inhibitors inhibited cancer-promoted angiogenesis in HIV-infected patients affected by Kaposi sarcoma. We aimed to evaluate the antineoplastic potential activities of the protease inhibitor indinavir (Crixivan) in in vitro and in vivo hepatocarcinoma models. We analyzed effects of indinavir on cell growth and invasiveness in Huh7 and SK-HEP-1 hepatocarcinoma cell lines and on in vivo tumor growth of the same cells in nude mice. Morphologic and molecular analyses on explanted tumors were carried out to evaluate vascularization and apoptosis. We observed a reduced ability to invade an in vitro extracellular matrix for both cell lines treated with indinavir compared with controls (P = 0,001). Moreover, indinavir treatment was able to inhibit matrix metalloproteinase-2 proteolytic activation, whereas there was no effect on cell proliferation. The drug was also able to delay in vivo tumor growth. The inhibition of tumor growth was statistically significant from days 6 to 21 (P = 0.004 and P = 0.003, respectively). Moreover, the drug showed anti...Continue Reading

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Citations

Sep 1, 2007·Current Opinion in Oncology·Dirk P Dittmer, Susan E Krown
Jun 13, 2012·Acta Oncologica·Fabio Martinon
Dec 30, 2008·The Lancet Oncology·Warren A ChowMin Guan
Aug 14, 2012·Journal of Cellular Physiology·Vincenzo EspositoAntonio Chirianni
Jul 6, 2016·Pharmacological Reports : PR·Sapna SharmaMilee Agarwal
Jun 13, 2020·Frontiers in Oncology·Giovanni Barillari
Mar 17, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Ladislav SivákMarek Kovář
Jul 3, 2021·Cancers·Christina PfabNahed El-Najjar
Apr 9, 2017·Oncology Research·Angelica PernaAntonio De Luca

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