Endostatin cDNA/cationic liposome complexes as a promising therapy to prevent lung metastases in osteosarcoma: study in a human-like rat orthotopic tumor.
Antiangiogenesis or destruction of tumor neovessels is an effective strategy to prevent tumor growth. Endostatin, one of the many inhibitors of angiogenesis that have been discovered, has shown conflicting results in preclinical assays. We studied the therapeutic potential of lipid/DNA complexes consisting of cationic liposomes and an endostatin-coding plasmid (Endo cDNA/CLP) in an orthotopic osteosarcoma model in rats. Empty plasmid without the endostatin gene complexed with cationic liposomes served as control. Animals were treated intravenously three times a week starting on the day tumors were detectable by (18)FDG tomoscintigraphy. During treatment, tumor progression was followed by PET scan and angioscintigraphy, and the effects of antivascular therapy on primary tumor, metastases, and tumor vascular density were confirmed by histologic analysis. Our results demonstrate that therapy using Endo cDNA/CLP is associated with pronounced delay in tumor growth. Moreover, it effectively prevented the occurrence of lung metastases, the major reason for bad prognosis and death in osteosarcoma patients. This approach could be used as an adjuvant therapy for osteosarcoma.
Dutour
Aurélie
A
Department of Medical Biochemistry and Molecular Biology, School of Medicine, University of Limoges, 87025 Limoges, France.
Monteil
Jacques
J
Paraf
François
F
Charissoux
Jean Louis
JL
Kaletta
Cortina
C
Sauer
Birgitta
B
Naujoks
Kurt
K
Rigaud
Michel
M
D000818:Animals; D002412:Cations / Q000737:chemistry; D049109:Cell Proliferation; D018076:DNA, Complementary / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D043169:Endostatins / Q000235:genetics / Q000378:metabolism*; D015316:Genetic Therapy; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000556:secondary*; D009362:Neoplasm Metastasis / Q000517:prevention & control; D012516:Osteosarcoma / Q000473:pathology*; D051381:Rats
D002412:Cations; D018076:DNA, Complementary; D043169:Endostatins; D008081:Liposomes