| Transfection of melanoma cells with antisense PAX3 oligonucleotides additively complements cisplatin-induced cytotoxicity. | |
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MedLine Citation:
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PMID: 15956257 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Advanced melanoma is difficult to treat, in part because of greater resistance to therapy compared with other cancer types. The mechanisms underlying this resistance are not well-understood. One factor that is reported to be involved in melanoma cell survival is PAX3, a transcription factor normally expressed during embryonic development, and which is critically required for development of neural crest-derivatives, including skin melanocytes. PAX3 expression is deregulated in primary melanomas and most melanoma cell lines. Here we have investigated whether targeting PAX3 expression in melanoma cell lines together with chemotherapeutic treatment increases susceptibility to therapeutic cell death. Using PAX3-specific antisense oligodeoxynucleotides (PAX3-AS) to treat melanoma cell lines in vitro, we showed dose-dependent reduction of proliferation of melanoma cells, and induction of apoptosis compared with control treatments. Induction of apoptosis was accompanied by the induction of active caspase-3 in UACC62 and M14 cells, and p53 protein in UACC62 cells. Treatment of melanoma cells with cisplatin induces DNA damage and cytotoxicity, which is thought to be via p53-dependent and -independent mechanisms. Treatment of either p53 mutant (M14) or wild-type (UACC62) melanoma cells with cisplatin, and varying doses of PAX3-AS, resulted in percentages of cells undergoing apoptosis equivalent to the sum of the individual treatments, irrespective of mutation status [e.g., UACC62, 43.8% (1 micromol/L PAX3-AS), 30.1% (20 micromol/L cisplatin), 69.6% (PAX3-AS + cisplatin); M14, 12.6% (1 micromol/L PAX3-AS), 41.5% (40 micromol/L cisplatin), 50.2% (PAX3-AS + cisplatin)]. These data suggest that treatment of melanoma cells with PAX3-AS complements cytotoxicity induced by cisplatin. |
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Authors:
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Shu-Jie He; Graham Stevens; Antony W Braithwaite; Michael R Eccles |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Molecular cancer therapeutics Volume: 4 ISSN: 1535-7163 ISO Abbreviation: Mol. Cancer Ther. Publication Date: 2005 Jun |
Date Detail:
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Created Date: 2005-06-15 Completed Date: 2005-09-26 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 101132535 Medline TA: Mol Cancer Ther Country: United States |
Other Details:
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Languages: eng Pagination: 996-1003 Citation Subset: IM |
Affiliation:
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Department of Pathology, Dunedin School of Medicine, New Zealand. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis Caspase 3 Caspases / metabolism Cell Line, Tumor Cell Proliferation / drug effects Cisplatin / toxicity* DNA-Binding Proteins / deficiency*, genetics*, metabolism Humans Immunohistochemistry Melanoma / genetics, metabolism*, pathology* Oligonucleotides, Antisense / genetics, metabolism* Paired Box Transcription Factors RNA, Messenger / genetics, metabolism Transcription Factors / deficiency*, genetics*, metabolism Transfection Tumor Suppressor Protein p53 / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/DNA-Binding Proteins; 0/Oligonucleotides, Antisense; 0/PAX3 protein, human; 0/Paired Box Transcription Factors; 0/RNA, Messenger; 0/Transcription Factors; 0/Tumor Suppressor Protein p53; 15663-27-1/Cisplatin; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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