Adenovirus-mediated inhibition of NF-κB confers chemo-sensitization and apoptosis in prostate cancer cells
Acquirement of multi-drug resistance by tumor cells represents a major obstacle in the management of prostate cancer. Such resistance was demonstrated in the androgen-independent DU-145 cells in response to paclitaxel and the mechanisms by which these cell develops resistance was not understood. The objective of this study was to examine whether abrogation of the constitutively active NF-κB in the chemoresistant, androgen independent DU-145 prostate cancer cells will enhance their sensitivity to cytototoxic agents. Inhibition of NF-κB by a dominant negative super-repressor IκB mutant adenoviral construct enhanced the apoptotic potentials of paclitaxel and rhTNF-α in these cells. Using reporter assays and RT-PCR analysis, we demonstrate that paclitaxel-induced cell death was associated with an increase in NF-κB activation and MDR-1 gene expression. Abrogation of these effects by the dominant negative IκB adenoviral construct suggests that induction and/or constitutive activation of NF-κB can block the paclitaxel-induced apoptotic signaling pathways in this cell line, possibly by increasing the expression of anti-apoptotic and MDR-1 gene products, leading to development of chemoresistance in these cells. We conclude that inhibition of NF-κB activation may have therapeutic implications for prostate cancer.
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Document Type: Research Article
Affiliations: Department of Urology, Tulane University Health Sciences Center, New Orleans, LA 70112, USA
Publication date: August 1, 2003
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- The International Journal of Oncology provides an international forum for the publication of the latest, cutting-edge research in the broad area of oncology and cancer treatment. The journal accepts original high quality works and reviews on all aspects of oncology research including carcinogenesis, metastasis, epidemiology, chemotherapy and viral oncology. Through fair and efficient peer review, the journal is dedicated to publishing top tier research in the field, offering authors rapid publication as well as high standards of copy-editing and production. The International Journal of Oncology is published on a monthly basis in both print and early online.
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