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Bcl-X(L) is a chemoresistance factor in human melanoma cells that can be inhibited by antisense therapy.
- Source :
-
International journal of cancer [Int J Cancer] 2002 May 01; Vol. 99 (1), pp. 29-34. - Publication Year :
- 2002
-
Abstract
- Malignant melanoma is a tumor that responds poorly to a variety of apoptosis-inducing treatment modalities, such as chemotherapy. The expression of genes that regulate apoptotic cell death plays an important role in determining the sensitivity of tumor cells to chemotherapeutic intervention. Bcl-x(L) is an antiapoptotic member of the Bcl-2 family and is universally expressed in human melanoma. To evaluate the Bcl-x(L) protein as a potential therapeutic target in melanoma, the influence of Bcl-x(L) expression levels on the chemoresistance of human melanoma cells was investigated. Overexpression of Bcl-x(L) in stably transfected human melanoma Mel Juso cells significantly reduced sensitivity to cisplatin-induced apoptosis (p < or = 0.05). In a parallel approach, reduction of Bcl-x(L) protein by specific AS oligonucleotide (ISIS 16009) treatment enhanced the chemosensitivity of Mel Juso cells by 62% compared to cells treated with MM control oligonucleotide (ISIS 16967) as well as chemotherapy-induced apoptosis. These data suggest that Bcl-x(L) is an important factor contributing to the chemoresistance of human melanoma. Reduction of Bcl-x(L) expression by AS oligonucleotides provides a rational and promising approach that may help to overcome chemoresistance in this malignancy.<br /> (Copyright 2002 Wiley-Liss, Inc.)
- Subjects :
- Blotting, Western
Cell Survival drug effects
Drug Resistance
Flow Cytometry
Humans
Melanoma pathology
Poly(ADP-ribose) Polymerases metabolism
Proto-Oncogene Proteins c-bcl-2 genetics
Skin Neoplasms pathology
Transfection
Tumor Cells, Cultured
bcl-X Protein
Antineoplastic Agents therapeutic use
Apoptosis drug effects
Cisplatin therapeutic use
Melanoma drug therapy
Oligonucleotides, Antisense therapeutic use
Proto-Oncogene Proteins c-bcl-2 antagonists & inhibitors
Skin Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 0020-7136
- Volume :
- 99
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- International journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 11948488
- Full Text :
- https://doi.org/10.1002/ijc.10248