c-Jun knockdown sensitizes osteosarcoma to doxorubicin.
The oncogene c-Jun has been found to be up-regulated in a variety of cancers, including osteosarcoma. Doxorubicin is a frontline chemotherapeutic against osteosarcoma, but is limited by toxicity. DNAzymes are oligonucleotides capable of specific catalysis of target mRNA. A biocompatible c-Jun DNAzyme nanoparticle formulated from chitosan regressed the growth and metastasis of pre-established tumors, especially in combination with doxorubicin. In vitro data confirmed that c-Jun knockdown chemosensitized these cells to doxorubicin treatment. c-Jun down-regulation-mediated tumor inhibition also led to concomitant decreased osteolysis. Clinically, knockdown of c-Jun with chitosan nanobiotechnology may proffer an improved treatment outcome for osteosarcoma.
Dass
Crispin R
CR
Department of Orthopaedics, St. Vincent's Hospital Melbourne, P.O. Box 2900, Fitzroy, Victoria 3065, Australia. cris.dass@yahoo.com
Khachigian
Levon M
LM
Choong
Peter F M
PF
D000818:Animals; D021881:DNA, Catalytic / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D051379:Mice; D010014:Osteolysis / Q000188:drug therapy / Q000473:pathology; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology; D016755:Proto-Oncogene Proteins c-jun / Q000172:deficiency*
D021881:DNA, Catalytic; D016755:Proto-Oncogene Proteins c-jun; D004317:Doxorubicin