Downregulation of c-jun results in apoptosis-mediated anti-osteosarcoma activity in an orthotopic model

被引：27

作者：

Dass, Crispin R. ^{[1
,2
]}

Friedhuber, Anna M. ^{[3
]}

Khachigian, Levon M. ^{[4
]}

Dunstan, Dave E. ^{[5
]}

Choong, Peter F. M. ^{[1
,2
,6
]}

机构：

[1] St Vincents Hosp, Dept Orthopaed, Fitzroy, Vic 3065, Australia

[2] Univ Melbourne, Dept Surg, Melbourne, Vic 3010, Australia

[3] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia

[4] UNSW & Prince Wales Hosp, Ctr Vasc Res, Sydney, NSW, Australia

[5] Univ Melbourne, Dept Chem & Biomol Engn, Melbourne, Vic 3010, Australia

[6] Peter MacCallum Canc Inst, Sarcoma Serv, Melbourne, Vic, Australia

来源：

CANCER BIOLOGY & THERAPY | 2008年 / 7卷 / 07期

关键词：

c-jun; cancer; apoptosis; deoxyribozyme; osteosarcoma; liposome;

D O I：

10.4161/cbt.7.7.6037

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 tumors originating in bone.

引用

页码：1033 / 1036

页数：4

共 17 条

[1] Brothers in arms - DNA enzymes, short interfering RNA, and the emerging wave of small-molecule nucleic acid-based gene-silencing strategies [J].

Bhindi, Ravinay ;

Fahmy, Roger G. ;

Lowe, Harry C. ;

Chesterman, Colin N. ;

Dass, Crispin R. ;

Cairns, Murray J. ;

Saravolac, Edward G. ;

Sun, Lun-Quan ;

Khachigian, Levon M. .

AMERICAN JOURNAL OF PATHOLOGY, 2007, 171 (04) :1079-1088

[2] A review of clinical and molecular prognostic factors in osteosarcoma [J].

Clark, Jonathan C. M. ;

Dass, Crispin R. ;

Choong, Peter F. M. .

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 2008, 134 (03) :281-297

[3] Cellular uptake, distribution, and stability of 10-23 deoxyribozymes [J].

Dass, CR ;

Saravolac, EG ;

Li, Y ;

Sun, LQ .

ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT, 2002, 12 (05) :289-299

[4] Liposomes containing cationic dimethyl dioctadecyl ammonium bromide: Formulation, quality control, and lipofection efficiency [J].

Dass, CR ;

Walker, TL ;

Burton, MA .

DRUG DELIVERY, 2002, 9 (01) :11-18

[5] Chitosan microparticles encapsulating PEDF plasmid demonstrate efficacy in an orthotopic metastatic model of osteosarcoma [J].

Dass, Crispin R. ;

Contreras, Karla G. ;

Dunstan, David E. ;

Choong, Peter F. M. .

BIOMATERIALS, 2007, 28 (19) :3026-3033

[6] A novel orthotopic murine model provides insights into cellular and molecular characteristics contributing to human osteosarcoma [J].

Dass, Crispin R. ;

Ek, Eugene T. ;

Contreras, Karla G. ;

Choong, Peter F. .

CLINICAL & EXPERIMENTAL METASTASIS, 2006, 23 (7-8) :367-380

[7] Pigment epithelium-derived factor overexpression inhibits orthotopic osteosarcoma growth, angiogenesis and metastasis [J].

Ek, E. T. H. ;

Dass, C. R. ;

Contreras, K. G. ;

Choong, P. F. M. .

CANCER GENE THERAPY, 2007, 14 (07) :616-626

[8] The role of high-dose therapy and autologous stem cell transplantation for pediatric bone and soft tissue sarcomas [J].

Ek, Eugene T. H. ;

Choong, Peter F. M. .

EXPERT REVIEW OF ANTICANCER THERAPY, 2006, 6 (02) :225-237

[9] Suppression of vascular permeability and inflammation by targeting of the transcription factor c-Jun [J].

Fahmy, Roger G. ;

Waldman, Alla ;

Zhang, Guishui ;

Mitchell, Ainslie ;

Tedla, Nicodemus ;

Cai, Hong ;

Geczy, Carolyn R. ;

Chesterman, Colin N. ;

Perry, Michael ;

Khachigian, Levon M. .

NATURE BIOTECHNOLOGY, 2006, 24 (07) :856-863

[10] Immunohistochemical detection of c-fos and c-jun expression in osseous and cartilaginous tumours of the skeleton [J].

Franchi, A ;

Calzolari, A ;

Zampi, G .

VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY, 1998, 432 (06) :515-519

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