linical Development lation Delivery of a Novel Diindolylmethane Derivative Ther the Treatment of Lung Cancer

nloaded purpose of this study was to determine the anticancer efficacy of 1,1-bis (3′-indolyl)-1-(p-biphenyl) ne (DIM-C-pPhC6H5) by inhalation delivery alone and in combination with i.v. docetaxel in a murine for lung cancer. An aqueous DIM-C-pPhC6H5 formulation was characterized for its aerodynamic propTumor-bearing athymic nude mice were exposed to nebulized DIM-C-pPhC6H5, docetaxel, or combinaIM-C-pPhC6H5 plus docetaxel) using a nose-only exposure technique. The aerodynamic properties ed mass median aerodynamic diameter of 1.8 ± 0.3 μm and geometric SD of 2.31 ± 0.02. Lung weight ion in mice treated with the drug combination was 64% compared with 40% and 47% in mice treated IM-C-pPhC6H5 aerosol and docetaxel alone, respectively. Combination treatment decreased expression , cyclin D1, survivin, Mcl-1, NF-κB, IκBα, phospho-IκBα, and vascular endothelial growth factor (VEGF) creased expression of c-Jun NH2-terminal kinase 2 and Bad compared with tumors collected from singletreatment and control groups. DNA fragmentationwas also enhanced inmice treatedwith the drug comn compared with docetaxel or DIM-C-pPhC6H5 alone. Combination treatment decreased expressions of and CD31 compared with single-agent treated and control groups. These results suggest that DIMC6H5 aerosol enhanced the anticancer activity of docetaxel in a lung cancer model by activating multiple ing pathways. The study provides evidence that DIM-C-pPhC6H5 can be used alone or in combination signal with other drugs for the treatment of lung cancer using the inhalation delivery approach.Mol Cancer Ther; 9(11); 3003–14. ©2010 AACR.