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Bcl‐X L is a chemoresistance factor in human melanoma cells that can be inhibited by antisense therapy
Author(s) -
HeereRess Elisabeth,
Thallinger Christiane,
Lucas Trevor,
SchlagbauerWadl Hermine,
Wacheck Volker,
Monia Brett P.,
Wolff Klaus,
Pehamberger Hubert,
Jansen Burkhard
Publication year - 2002
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10248
Subject(s) - melanoma , apoptosis , cancer research , transfection , chemotherapy , malignancy , biology , oligonucleotide , cisplatin , antisense therapy , programmed cell death , cell culture , gene , genetics , locked nucleic acid
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 ≤ 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. © 2002 Wiley‐Liss, Inc.