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A7095 - Vascular Endothelial Growth Factor Knockdown by Intratracheal Administration of Small-Interfering RNA Dry Powder Inhibits Tumor Growth in a Mouse Lung Metastasis Model
Author Block: K. Miwata1, Y. Horimasu1, T. Masuda1, S. Miyamoto1, T. Nakashima1, H. Iwamoto1, K. Fujitaka1, H. Hamada2, N. Hattori1; 1Department of Molecular and Internal Medicine, Hiroshima University, Hiroshima, Japan, 2Department of Physical Analysis and Therapeutic Sciences, Hiroshima University, Hiroshima, Japan.
Rationale: The use of small-interfering RNA (siRNA) as an inhalation therapy is expected to powerful therapeutic strategy for lung cancer because of its high gene silencing effect and sequence specificity. Three types of inhalation systems are clinically used: pressurized metered dose inhalers (MDIs), nebulizers, and dry powder inhalers (DPIs). Among them, DPIs has received much attention because of their low cost, portability and good preservability. Previous studies reported that intratracheal administration of siRNA by MDIs or nebulizers could suppress tumor growth in a lung metastatic model mice, however the effect of siRNA dry powders have not been elucidated. Methods: To evaluate gene silencing effect and anti-tumor effect by intratracheal administration of siRNA dry powder, vascular endothelial growth factor (VEGF)-specific-siRNA (VEGF-siRNA) dry powder were administered intratracheally to mice carrying metastatic lung tumors consisting of B16F10 melanoma cells or Lewis lung carcinoma cells. First, we evaluated gene silencing effect by measuring VEGF amount in bronchoalveolar lavage fluid (BALF) and VEGF expression in immunohistochemical staining lung tumor tissue. Thereafter, the number of visible foci on the surfaces of the lungs and tumor area in lung tumor sections were measured to evaluate anti-tumor effect. Results: Single intratracheal administration of VEGF-siRNA dry powder reduced VEGF amount in BALF and VEGF expression in lung tumor tissue. Furthermore, repeated intratracheal administration of VEGF-siRNA dry powder inhibited tumor growth in lung. Conclusions: Intratracheal administration of VEGF-siRNA dry powder suppressed gene expression in lung tumor and inhibited tumor growth in lung. Taken together, intratracheal administration of siRNA dry powder may become a novel therapeutic strategy for lung cancer through specific gene suppression in lung tumor tissue.