Bcl‐XL is a chemoresistance factor in human melanoma cells that can be inhibited by antisense therapy

• Published in: International journal of cancer 2002-05, Vol.99 (1), p.29-34
• Main Authors: Heere‐Ress, Elisabeth, Thallinger, Christiane, Lucas, Trevor, Schlagbauer‐Wadl, Hermine, Wacheck, Volker, Monia, Brett P., Wolff, Klaus, Pehamberger, Hubert, Jansen, Burkhard
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; antisense oligonucleotide; apoptosis; Bcl‐xL; Biological and medical sciences; chemoresistance; General aspects; Medical sciences; melanoma; Pharmacology. Drug treatments
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.10248

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‐xL is an antiapoptotic member of the Bcl‐2 family and is universally expressed in human melanoma. To evaluate the Bcl‐xL protein as a potential therapeutic target in melanoma, the influence of Bcl‐xL expression levels on the chemoresistance of human melanoma cells was investigated. Overexpression of Bcl‐xL 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‐xL 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‐xL is an important factor contributing to the chemoresistance of human melanoma. Reduction of Bcl‐xL expression by AS oligonucleotides provides a rational and promising approach that may help to overcome chemoresistance in this malignancy. © 2002 Wiley‐Liss, Inc.