Construction of recombinant lentivirus vector for tumor vasoinhibitory peptide alphastatin gene delivery.

Angiogenesis is a prerequisite for tumor progression and metastasis. Alphastatin, as an endogenous angiogenesis inhibitor, was recently used as an anticancer agent in several tumor models. We constructed recombinant self-inactivating lentivirus vectors expressing alphastatin and evaluated their ability to transfer genes into human umbilical vein endothelial cells (HUVECs) as well as their antiangiogenic activities in vitro. Recombinant self-inactivating lentiviral vectors efficiently and stably transduced endothelial cells, and lentivirus-transduced HUVECs were capable of sustainedly secreting the antiangiogenesis peptide alphastatin. Long-term expression and secretion of alphastatin resulted in significant inhibition of endothelial cell angiogenesis induced by vascular endothelial growth factor. This report presents the first use of lentivirus-based vectors to deliver the endogenous angiogenesis inhibitor alphastatin, and suggests the potential utility of antiangiogenic gene therapy with lentiviral vectors for the treatment of cancer.