Source: Annual Congress 2010 - Pathology of lung cancer
Disease area: Thoracic oncology

Abstract

Background: We have previously shown that airway epithelial nuclear factor (NF)-κB activation promotes urethane-induced lung inflammation and carcinogenesis. The proteasome inhibitor bortezomib blocks NF-κΒ in various cell types.
Aim: To determine the effects of bortezomib on urethane-induced lung inflammation and carcinogenesis.
Methods: For induction of multi-stage lung adenocarcinogenesis, Balb/c mice received four weekly intraperitoneal injections of urethane (1 g/kg). Intraperitoneal bi-weekly bortezomib (1mg/kg) was administered during tumor initiation, progression, or continuously (weeks 0-4, 16-20, and 0-24 post-urethane, respectively). Primary end-points were lung tumor number, size, and histologic distribution at 24 weeks.
Results: Short-term bortezomib treatment during tumor initiation (weeks 0-4) or tumor progression (weeks 16-20) had no profound effect on the number, size, and type of lung tumors. However, continuous bortezomib treatment of urethane-treated mice resulted in markedly increased lung tumor number and size after 24 weeks, without affecting the histologic distribution of lung neoplastic lesions between hyperplasia, adenoma, and adenocarcinoma. Studies of urethane and bortezomib-treated mice at early time points revealed that bortezomib suppressed the acute (at 1 week), but augmented and perpetuated the chronic (at 4 weeks) inflammatory response to urethane.
Conclusion: Prolonged proteasome inhibition enhances chemical lung carcinogenesis in mice and may promote lung cancer progression in humans.
Acknowledgements: Thorax Foundation, Athens, Greece; US NIH HL61419, and the US Department of Veterans Affairs.

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S. P. Karabela, C. A. Kairi, I. Psallidas, F. McMahon, L. A. Gleaves, W. Han, S. Vassiliou, C. Roussos, I. Kalomenidis, F. E. Yull, S. G. Zakynthinos, T. S. Blackwell, G. T. Stathopoulos (Patra, Greece; Nashville, United States Of America). Long-term proteasome inhibition promotes chemical lung carcinogenesis. Eur Respir J 2010; 36: Suppl. 54, 3271

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