c-Jun knockdown sensitizes osteosarcoma to doxorubicin.

Abstract

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.

• Authors: Crispin R Dass, Levon M Khachigian, Peter F M Choong
• Journal: Molecular cancer therapeutics (Mol Cancer Ther) Vol. 7 Issue 7 Pg. 1909-12 (Jul 2008) ISSN: 1535-7163 [Print] United States
• PMID: 18645001 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Catalytic
• Proto-Oncogene Proteins c-jun
• Doxorubicin

Topics

• Animals
• DNA, Catalytic (pharmacology)
• Doxorubicin (pharmacology, therapeutic use)
• Drug Screening Assays, Antitumor
• Drug Synergism
• Humans
• Mice
• Osteolysis (drug therapy, pathology)
• Osteosarcoma (drug therapy, pathology)
• Proto-Oncogene Proteins c-jun (deficiency)