Specific effects of bortezomib against experimental malignant pleural effusion: a preclinical study

Treatment of LLC cells with low concentrations of bortezomib (100 ng/ml) inhibited NF-κB activation and NF-κB-dependent transcription, but not cellular proliferation. Bortezomib treatment of immunocompetent C57BL/6 mice bearing LLC-induced subcutaneous tumors and MPEs significantly blocked tumor-specific NF-κB activation. However, bortezomib treatment did not impair subcutaneous LLC tumor growth, but was effective in limiting LLC-induced MPE. This specific effect was evidenced by significant reductions in effusion accumulation and the associated mortality and was observed with both preventive (beginning before MPE formation) and therapeutic (beginning after MPE establishment) bortezomib treatment. The favorable impact of bortezomib on MPE was associated with suppression of cardinal MPE-associated phenomena, such as inflammation, vascular hyperpermeability, and angiogenesis. In this regard, therapeutic bortezomib treatment had identical favorable results on MPE compared with preventive treatment, indicating that the drug specifically counteracts effusion formation.These studies indicate that proteasome inhibition tailored to block NF-κB activation of lung adenocarcinoma specifically targets the effusion-inducing phenotype of this tumor. Although the drug has limited activity against advanced solid lung cancer, it may prove beneficial for patients with MPE.A malignant pleural effusion (MPE) affects one in seven patients with cancer, most commonly lung or breast adenocarcinoma [1,2]. For these patients, MPE has severe consequences: it prohibits surgical cure and portends short and cumbersome survival [3]. Current treatments against MPE (pleural evacuation or pleurodesis) [1,2,4,5] are associated with hospital stay, interventional procedures, morbidity and mortality, and benefit only select patients [1-8]. Towards improving current practice against MPE, a better understanding of its pathogenesis is required, which may aid in developing effective strategies to block pleu