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Mol Cancer Ther. 2008 Jul;7(7):1909-12. doi: 10.1158/1535-7163.MCT-08-0086.

c-Jun knockdown sensitizes osteosarcoma to doxorubicin.

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  • 1Department of Orthopaedics, St. Vincent's Hospital Melbourne, P.O. Box 2900, Fitzroy, Victoria 3065, Australia. cris.dass@yahoo.com

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.

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