BACKGROUND: We have previously shown that nuclear factor (NF)-kappaB activation 
of mouse Lewis lung carcinoma (LLC) specifically promotes the induction of 
malignant pleural effusions (MPE) by these cells. In the present studies we 
hypothesized that treatment of immunocompetent mice with bortezomib tailored to 
inhibit cancer cell NF-kappaB activation and not proliferation specifically 
inhibits MPE formation by LLC cells.
RESULTS: Treatment of LLC cells with low concentrations of bortezomib (100 
ng/ml) inhibited NF-kappaB activation and NF-kappaB-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-kappaB 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.
CONCLUSIONS: These studies indicate that proteasome inhibition tailored to block 
NF-kappaB 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.