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Proteasome Inhibition Sensitizes Prostate Cancer Cells to TRAIL‐Induced Cell Death In Vivo
Author(s) -
Christian Perry A,
Thorpe Jeffery A,
Schwarze Steven R
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.339
Subject(s) - lncap , bortezomib , cancer research , prostate cancer , apoptosis , proteasome inhibitor , in vivo , cancer , cancer cell , programmed cell death , carfilzomib , proteasome , medicine , multiple myeloma , chemistry , biology , microbiology and biotechnology , biochemistry
The goal of this study is to investigate the anti‐neoplastic capability of proteasome inhibition to synergize with a death receptor agonist in vivo . Proteasome inhibition, by the small molecule inhibitor Velcade (Bortezomib), is currently approved for the clinical treatment of Multiple Myeloma. Numerous cancer cells exhibit significant resistance to AICD (Antigen‐Induced Cell Death)‐mediated apoptosis. An AICD‐resistant LNCaP prostate cancer xenograft model was used to determine the efficacy of proteasome inhibition in sensitizing cancer cells to apoptosis in vivo . Mice treated with a combination of Velcade and TRAIL (TNF‐Related Apoptosis Inducing Ligand) showed a decrease in tumor volume as well as loss of the hemorrhagic phenotype associated with LNCaP xenografts. Immunohistochemical analysis showed that combining Velcade and TRAIL produced a more differentiated tumor, decreased tumor cell proliferation and increased tumor cell apoptosis. This study suggests that proteasome inhibition in combination with the apoptosis inducing ligand TRAIL may have efficacy in the treatment of prostate cancer. Source of research support: University of Kentucky Markey Cancer Center and the University of Kentucky Vice President for Research