Inhalation therapy using small-interfering RNA (siRNA) is a potentially effective therapeutic strategy for lung cancer because of its high gene-silencing effects and sequence specificity. Previous studies reported that intratracheal administration of siRNA using pressurized metered dose inhalers or nebulizers could suppress tumor growth in murine lung metastatic models. Although dry powder inhalers are promising devices due to their low cost, good portability, and preservability, the anti-tumor effects of siRNA dry powder have not been elucidated. To evaluate the gene-silencing and anti-tumor effects of intratracheally delivered siRNA dry powder, vascular endothelial growth factor-specific siRNA (VEGF-siRNA) dry powder was administered intratracheally to mice with metastatic lung tumors consisting of B16F10 melanoma cells or Lewis lung carcinoma cells. A single intratracheal administration of VEGF-siRNA dry powder reduced VEGF levels in both bronchoalveolar lavage fluid and lung tumor tissue. Furthermore, repeated intratracheal administration of VEGF-siRNA dry powder suppressed the number of visible metastatic foci on the lung surface and tumor area in lung tissues. Taken together, intratracheal administration of siRNA dry powder could be a novel therapeutic strategy for lung cancer through the suppression of specific genes expressed in lung tumor tissue.

使用小干扰RNA（siRNA）的吸入疗法是一种潜在的有效肺癌治疗策略，因为它具有很高的基因沉默效果和序列特异性。先前的研究报道，使用加压定量吸入器或雾化器气管内施用siRNA可以抑制小鼠肺转移模型中的肿瘤生长。尽管干粉吸入器因其低成本，良好的便携性和可保存性而成为有前途的设备，但尚未阐明siRNA干粉的抗肿瘤作用。为了评估气管内递送的siRNA干粉的基因沉默和抗肿瘤作用，将血管内皮生长因子特异性siRNA（VEGF-siRNA）干粉经气管内给药至具有由B16F10黑色素瘤细胞或Lewis肺癌细胞组成的转移性肺肿瘤的小鼠。气管内注射VEGF-siRNA干粉可降低支气管肺泡灌洗液和肺肿瘤组织中的VEGF水平。此外，反复气管内施用VEGF-siRNA干粉抑制了肺表面和肺组织肿瘤区域中可见转移灶的数量。综上所述，通过抑制在肺肿瘤组织中表达的特定基因，气管内施用siRNA干粉可能是肺癌的一种新型治疗策略。气管内注射VEGF-siRNA干粉可降低支气管肺泡灌洗液和肺肿瘤组织中的VEGF水平。此外，反复气管内施用VEGF-siRNA干粉抑制了肺表面和肺组织肿瘤区域中可见转移灶的数量。综上所述，通过抑制在肺肿瘤组织中表达的特定基因，气管内施用siRNA干粉可能是肺癌的一种新型治疗策略。气管内注射VEGF-siRNA干粉可降低支气管肺泡灌洗液和肺肿瘤组织中的VEGF水平。此外，反复气管内施用VEGF-siRNA干粉抑制了肺表面和肺组织肿瘤区域中可见转移灶的数量。综上所述，通过抑制在肺肿瘤组织中表达的特定基因，气管内施用siRNA干粉可能是肺癌的一种新型治疗策略。