Antiangiogenic liposomal gene therapy with 16K human prolactin efficiently reduces tumor growth.
Human 16K PRL (16K hPRL) is a potent inhibitor of angiogenesis both in vitro and in vivo. It has been shown to prevent tumor growth in three xenograft mouse models. Here we have used a gene transfer method based on cationic liposomes to produce 16K hPRL and demonstrate that 16K hPRL inhibits tumor growth in a subcutaneous B16F10 mouse melanoma model. Computer-assisted image analysis shows that 16K hPRL treatment results in the reduction of tumor vessel length and width, leading to a 57% reduction in average vessel size. We thus show, for the first time, that administration of the 16K hPRL gene complexed to cationic liposomes is effective to maintain antiangiogenic activities of 16K hPRL level.
Kinet
Virginie
V
GIGA-Research, Molecular Biology and Genetic Engineering Unit, University of Liège, 4000 Sart Tilman, Belgium.
Nguyen
Ngoc-Quynh-Nhu
NQ
Sabatel
Céline
C
Blacher
Silvia
S
Noël
Agnès
A
Martial
Joseph A
JA
Struman
Ingrid
I
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D002412:Cations; D002460:Cell Line; D002784:Cholesterol; D004274:DNA, Recombinant / Q000008:administration & dosage / Q000627:therapeutic use*; D004354:Drug Screening Assays, Antitumor; D005229:Fatty Acids, Monounsaturated; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D007668:Kidney; D008055:Lipids; D008081:Liposomes; D008546:Melanoma, Experimental / Q000098:blood supply / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D011388:Prolactin / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use*; D000644:Quaternary Ammonium Compounds; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000502:physiology; D014162:Transfection / Q000379:methods
D020533:Angiogenesis Inhibitors; D002412:Cations; D004274:DNA, Recombinant; D005229:Fatty Acids, Monounsaturated; D008055:Lipids; C086724:Lipofectamine; D008081:Liposomes; D000644:Quaternary Ammonium Compounds; D011993:Recombinant Fusion Proteins; D011388:Prolactin; D002784:Cholesterol; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane