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[Cancer Research 59, 3308-3312, July 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 3308-3312, July 15, 1999]
© 1999 American Association for Cancer Research

Advances in Brief

Liposomes Complexed to Plasmids Encoding Angiostatin and Endostatin Inhibit Breast Cancer in Nude Mice1

Qing-Rong Chen, Dhruv Kumar, Sanford A. Stass and A. James Mixson2

Department of Pathology and Greenebaum Cancer Center, University of Maryland, Baltimore, Maryland 21201 [Q-R. C., S. A. S., A. J. M.], and Department of Pathology, Sinai Hospital of Baltimore, Baltimore Maryland 21215 [D. K.]

Gene therapy transfer of angiostatin and endostatin represents an alternative method of delivering angiogenic polypeptide inhibitors. We examined whether liposomes complexed to plasmids encoding angiostatin or endostatin inhibited angiogenesis and the growth of MDA-MB-435 tumors implanted in the mammary fat pads of nude mice. We determined that plasmids expressing angiostatin (PCI-Angio) or endostatin (PCI-Endo) effectively reduced angiogenesis using an in vivo Matrigel assay. We then investigated the efficacy of these plasmids in reducing the size of tumors implanted in the mammary fat pad of nude mice. Both PCI-Angio and PCI-Endo significantly reduced tumor size when injected intratumorally (P < 0.05). Compared to the untreated control group, the mice treated with PCI-Angio and PCI-Endo exhibited a reduction in tumor size of 36% and 49%, respectively. In addition, we found that i.v. injections of liposomes complexed to PCI-Endo reduced tumor growth in the nude mice by nearly 40% when compared to either empty vector (PCI) or untreated controls (P < 0.05). These findings provide a basis for the further development of nonviral delivery of antiangiogenic genes.




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Copyright © 1999 by the American Association for Cancer Research.