Vasculature-targeted tumor necrosis factor-alpha increases the therapeutic index of doxorubicin against prostate cancer

Maria T S Bertilaccio, Matteo Grioni, Brent W. Sutherland, Elena Degl'Innocenti, Massimo Freschi, Elena Jachetti, Norman M. Greenberg, Angelo Corti, Matteo Bellone

Research output: Contribution to journalArticle

Abstract

BACKGROUND. Poor penetration and uneven distribution of doxorubicin in tumors limits the efficacy of this drug in patients with prostate cancer (PC). Aim of the study was to investigate whether pre-treatment with NGR-TNF, a tumor necrosis factor-α derivative able to target tumor vessels and alter vessel permeability, increases the penetration and the efficacy of doxorubicin in pre-clinical models of PC. METHODS. Wild type C57BL/6 mice bearing androgen-independent TRAMP-C1 PC and transgenic adenocarcinoma of the mouse prostate (TRAMP) mice, which spontaneously develop PC and metastasis, were treated with repeated cycles of doxorubicin, administered either alone or following NGR-TNF. Tumor growth and drug uptake by cancer cells was evaluated. RESULTS. Doxorubicin as a single agent blocked the growth of TRAMP-C1 cells in vitro but not in vivo. Pre-treatment of mice bearing subcutaneous TRAMP-C1 tumors with NGR-TNF favored doxorubicin penetration into the tumor mass, and in both TRAMP-C1 and TRAMP models significantly delayed tumor growth without increasing drug-related toxicity. CONCLUSIONS. Pre-treatment with NGR-TNF significantly expanded the therapeutic index of doxorubicin in mouse models of hormone-dependent and -independent PC.

Original languageEnglish
Pages (from-to)1105-1115
Number of pages11
JournalProstate
Volume68
Issue number10
DOIs
Publication statusPublished - Jul 1 2008

Keywords

  • Androgen-independent
  • CD13
  • Chemotherapy
  • Cytokines
  • Mouse model
  • TRAMP

ASJC Scopus subject areas

  • Urology

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    Bertilaccio, M. T. S., Grioni, M., Sutherland, B. W., Degl'Innocenti, E., Freschi, M., Jachetti, E., Greenberg, N. M., Corti, A., & Bellone, M. (2008). Vasculature-targeted tumor necrosis factor-alpha increases the therapeutic index of doxorubicin against prostate cancer. Prostate, 68(10), 1105-1115. https://doi.org/10.1002/pros.20775