| Targeting inhibitor of apoptosis proteins in combination with dacarbazine or TRAIL in melanoma cells. | |
| | |
MedLine Citation:
|
PMID: 21508672 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Melanoma is a highly aggressive malignant tumor with an exceptional ability to develop resistance and no curative therapy is available for patients with distant metastatic disease. The inhibitor of apoptosis protein (IAP) family has been related to therapy resistance in cancer. We examined the importance of the IAPs in the resistance to the commonly used chemotherapeutic agent dacarbazine (DTIC) and the apoptosis inducer TRAIL (TNF-related apoptosis inducing ligand) in malignant melanoma. The data presented show that the expression of IAPs is universal, concomitant and generally high in melanoma cell lines and in patient samples. Depleting IAP expression by siRNA tended to reduce cell viability, with XIAP reduction being the most efficient in all four cell lines examined (FEMX-1, LOX, SKMEL-28 and WM115). The combined treatment of XIAP siRNA and DTIC showed a weak improvement in two of four cell lines, while all four cell lines showed enhanced sensitivity towards TRAIL (AdhCMV-TRAIL) after XIAP depletion. In addition, cIAP-1, cIAP-2 and survivin down-regulation sensitized to TRAIL treatment in several of the cell lines. Cells exposed to TRAIL and XIAP siRNA showed increased DNA-fragmentation and cleavage of Bid, procaspase-8, -9, -7 and -3 and PARP, and change in the balance between pro- and anti-apoptotic proteins, indicating an enhanced level of apoptosis. Furthermore, the combined treatment reduced the ability of melanoma cells to engraft and form tumors in mice, actualizing the combination for future therapy of malignant melanoma. |
| | |
Authors:
|
Birgit O Engesæter; Menaka Sathermugathevan; Tina Hellenes; Olav Engebråten; Ruth Holm; Vivi Ann Flørenes; Gunhild M Mælandsmo |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-7-01 |
Journal Detail:
|
Title: Cancer biology & therapy Volume: 12 ISSN: 1555-8576 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
|
Created Date: 2011-4-21 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 101137842 Medline TA: Cancer Biol Ther Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Oral ingestion of Streptococcus thermophilus does not affect mucositis severity or tumor progression...
Next Document: Immunogenicity, safety and tolerability of monovalent 2009 pandemic influenza A/H1N1 MF59-adjuvanted...