Downregulation of c-jun results in apoptosis-mediated anti-osteosarcoma activity in an orthotopic model.
c-jun has been found to be upregulated in a variety of cancers including osteosarcoma. DNAzymes are oligonucleotides capable of specific downregulation of target genes. c-jun knockdown-mediated apoptosis in osteosarcoma cells involved caspases-1, -2 and -8, but not the Fas/FasL pathway. A c-jun DNAzyme, encapsulated within a novel cationic multilamellar vesicle liposome, inhibited the growth and metastasis of osteosarcoma in an orthotopic spontaneously metastasising model of the disease. The 60 nm DDAB:DOPE liposome was formulated using ethanol injection/extrusion. Clinically, downregulation of c-jun may proffer an improved treatment outcome for these tumours originating in bone.
Dass
Crispin R
CR
Department of Orthopaedics and University of Melbourne Department of Surgery, St. Vincent's Hospital, Victoria, Australia. cris.dass@yahoo.com
Friedhuber
Anna M
AM
Khachigian
Levon M
LM
Dunstan
Dave E
DE
Choong
Peter F M
PF
D000818:Animals; D017209:Apoptosis; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry; D021881:DNA, Catalytic / Q000737:chemistry*; D018450:Disease Progression; D015536:Down-Regulation; D006801:Humans; D008027:Light; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D012516:Osteosarcoma / Q000188:drug therapy / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D012542:Scattering, Radiation
D021881:DNA, Catalytic; D008081:Liposomes; D016755:Proto-Oncogene Proteins c-jun; D004247:DNA