Abstract
Background: Anti-apoptotic Bcl-2 family proteins, such as Bcl-2 and Bcl-x, can modulate radio- and/or chemosensitivity of human malignancies. Since no information is available on the role Mcl-1 may play in the radioresponse of tumor cells, the relationship between Mcl-1 expression and response to ionizing radiation (IR) was investigated using an antisense strategy. Materials and Methods: Human melanoma cells were treated with Mcl-1 antisense oligonucleotides (ASOs) and IR. The effects of antisense treatment alone or in combination with IR on proliferation, induction of apoptosis and clonogenic cell death were evaluated. Results: ASO treatment in combination with IR reduced the mean cell numbers 9.5-fold compared to a 2.6-fold reduction after ASO treatment alone and a 1.6-fold reduction after IR alone. The percentages of apoptosis measured (means±SD) were 49%±3.0 in antisense/IR-treated cultures compared to 1.3%±0.5, 14.3%±0.5, 7.3%±1.1 and 10.3%±0.6 in ASO controls, in antisense-treated, in IR-treated and in antisense control plus IR-treated cells, respectively. Colony formation assays demonstrated a synergistic effect of Mcl-1 down-regulation with IR. Conclusion: Mcl-1 expression affects the radioresistance of human melanoma cells.
Footnotes
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↵* Hans Skvara and Christiane Thallinger should be regarded as equal contributors.
- Received December 6, 2004.
- Accepted April 25, 2005.
- Copyright© 2005 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved