Gene therapy with p53 and a fragment of thrombospondin I inhibits human breast cancer in vivo.
We recently reported that a p53 encoding plasmid (BAP-p53) complexed to liposomes administered intravenously markedly attenuates the growth of a malignant human breast tumor. We now have found that systemically delivered liposomes complexed to a plasmid expressing an established antiangiogenic peptide of thrombospondin I (BAP-TSPf) decreased the growth of MDA-MB-435 tumors compared to controls in nude mice. Compared to BAP-p53, the BAP-TSPf group had a similar antitumor efficacy. More importantly, liposomes complexed with BAP-TSPf and BAP-p53 synergistically decreased the growth of MDA-MB-435 tumors when compared to either BAP-p53 or BAP-TSPf alone. Furthermore, we also determined that the combination therapy of p53 and TSPf inhibited endothelial cells in vitro more than either p53 or TSPf alone. There was also a significant decrease of the blood vessel density in the combination p53 and TSPf treatment group compared to the control groups. These results suggest that liposomes complexed to a tumor suppressor and antiangiogenic genes may be effective in treating metastatic tumors.
Xu
M
M
Department of Pathology, University of Maryland at Baltimore 21201, USA.
Kumar
D
D
Stass
S A
SA
Mixson
A J
AJ
D000818:Animals; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007275:Injections, Intravenous; D008081:Liposomes / Q000627:therapeutic use; D008325:Mammary Neoplasms, Experimental / Q000628:therapy*; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010446:Peptide Fragments / Q000235:genetics / Q000627:therapeutic use; D019700:Thrombospondin 1 / Q000235:genetics / Q000627:therapeutic use*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000627:therapeutic use*
D008081:Liposomes; D010446:Peptide Fragments; D019700:Thrombospondin 1; D016159:Tumor Suppressor Protein p53