The purpose of this study was to determine the anticancer efficacy of 1,1-bis (3'-indolyl)-1-(p-biphenyl) methane (DIM-C-pPhC₆H₅) by inhalation delivery alone and in combination with i.v.
docetaxel in a murine model for
lung cancer. An aqueous DIM-C-pPhC₆H₅ formulation was characterized for its aerodynamic properties.
Tumor-bearing athymic nude mice were exposed to nebulized DIM-C-pPhC₆H₅,
docetaxel, or combination (DIM-C-pPhC₆H₅ plus
docetaxel) using a nose-only exposure technique. The aerodynamic properties included mass median aerodynamic diameter of 1.8 ± 0.3 μm and geometric SD of 2.31 ± 0.02. Lung
weight reduction in mice treated with the
drug combination was 64% compared with 40% and 47% in mice treated with DIM-C-pPhC₆H₅
aerosol and
docetaxel alone, respectively. Combination treatment decreased expression of Akt,
cyclin D1,
survivin, Mcl-1, NF-κB, IκBα, phospho-IκBα, and
vascular endothelial growth factor (
VEGF) and increased expression of c-Jun NH₂-terminal
kinase 2 and Bad compared with
tumors collected from single-agent treatment and control groups. DNA fragmentation was also enhanced in mice treated with the
drug combination compared with
docetaxel or DIM-C-pPhC₆H₅ alone. Combination treatment decreased expressions of
VEGF and CD31 compared with single-agent treated and control groups. These results suggest that DIM-C-pPhC₆H₅
aerosol enhanced the anticancer activity of
docetaxel in a
lung cancer model by activating multiple signaling pathways. The study provides evidence that DIM-C-pPhC₆H₅ can be used alone or in combination with other drugs for the treatment of
lung cancer using the inhalation delivery approach.