Growth of human melanoma xenografts is suppressed by systemic angiostatin gene therapy

Monica Rodolfo, Enrica Mira Catò, Sabina Soldati, Roberta Ceruti, Marco Asioli, Eugenio Scanziani, Paolo Vezzoni, Giorgio Parmiani, Maria Grazia Sacco

Research output: Contribution to journalArticlepeer-review

Abstract

The effect of local and systemic delivery of the angiostatin gene on human melanoma growth was studied in nude mice. Liposome-coated plasmids carrying the cDNA coding for murine and human angiostatin (CMVang and BSHang) were injected weekly, locally or systemically, in mice transplanted with melanoma cells. The treatment reduced melanoma growth by 50% to 90% compared to that occurring in control animals treated with liposome-coated plasmid carrying the lacZ gene or in untreated controls. The growth of both locally injected and controlateral uninjected tumors in mice bearing two melanoma grafts was significantly suppressed after intratumoral treatment. Tumor growth inhibition was also observed in mice treated by intraperitoneal delivery, suggesting that angiostatin gene therapy acts through a systemic effect. Both melanoma growth suppression and delay in the onset of tumor growth were observed in treated mice. PCR performed on tumors and normal tissues showed that the lipofected DNA was present in tissues from treated mice, and angiostatin expression was demonstrated by RT-PCR. Histopathological analysis of melanoma nodules revealed an increase in apoptotic cells and a reduction in vessel density in tumors from treated mice. Our results suggest that systemic, liposome-mediated administration of genes coding for antiangiogenic factors represents a promising strategy for melanoma treatment in humans.

Original languageEnglish
Pages (from-to)491-496
Number of pages6
JournalCancer Gene Therapy
Volume8
Issue number7
DOIs
Publication statusPublished - 2001

Keywords

  • Angiostatin
  • Gene therapy
  • Liposomes
  • Melanoma

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

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