Gene therapy with Plasmid
AMEP (antiangiogenic metargidin
peptide) has recently been studied as a potential targeted
therapy for
melanoma. This plasmid is designed to downregulate α5β1 and αvβ3
integrins. In our study, electroporation was used as a nonviral delivery system. We investigated the antiangiogenic and direct antitumor effectiveness of this gene therapy on low and highly metastatic
B16 melanoma variants. In vitro, the antiangiogenic effectiveness as determined by tube formation assay on endothelial cells was predominantly dependent on
AMEP expression levels. In vivo, antitumor effectiveness was mediated by the inhibition of proliferation, migration and invasion of
melanoma cells and correlated with the expression of
integrins on
tumor cells after intratumor delivery. In addition, reduced metastatic potential was shown. Intramuscular gene electrotransfer of Plasmid
AMEP, for
AMEP systemic distribution, had no antitumor effect with this specific preventive treatment protocol, confirming that direct
tumor delivery was more effective. This study confirms our previous in vitro data that the expression levels of
integrins on
melanoma cells could be used as a
biomarker for antitumor effectiveness in
integrin-targeted
therapies, whereas the expression levels of
AMEP peptide could be a predictive factor for antiangiogenic effectiveness of Plasmid
AMEP in the treatment of
melanoma.