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Suppression of tobacco carcinogen-induced lung tumorigenesis by aerosol-delivered glycerol propoxylate triacrylate-spermine copolymer/short hairpin Rab25 rna complexes in female A/J mice

Cited 3 time in Web of Science Cited 4 time in Scopus
Authors
Gankhuyag, Nomundelger; Yu, Kyeong Nam; Davaadamdin, Orkhonselenge; Lee, Somin; Cho, Won Young; Park, Changhoon; Jiang, Hu-Lin; Singh, Bijay; Chae, Chan-Hee; Cho, Myung-Haing; Cho, Chong-Su
Issue Date
2017-04
Citation
Journal of Aerosol Medicine and Pulmonary Drug Delivery, Vol.30 No.2, pp.81-90
Keywords
aerosol-delivered shRab25AJ micelung cancerNNKgene therapy
Abstract
Background: Rab25, a member of Rab family of small guanosine triphosphatase, is associated with progression of various types of human cancers, including lung cancer, the leading cause of cancer-associated deaths around the globe. Methods: In this study, we report the gene therapeutic effect of short hairpin Rab25 RNA (shRab25) on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in female A/J mice. Initially, mice (6 weeks old) were injected with single dose of NNK (2mg/0.1mL saline/mouse) by intraperitoneal injection to induce the tumor. Eight weeks later, shRab25 was complexed with glycerol propoxylate triacrylate-spermine (GPT-SPE) copolymer and delivered into tobacco-induced lung cancer models through a nose-only inhalation system twice a week for 2 months. Results: GPT-SPE/shRab25 largely decreased the tobacco-induced tumor numbers and tumor volume in the lungs compared to GPT-SPE- or GPT-SPE/shScr-delivered groups. Remarkably, aerosol-delivered GPT-SPE/shRab25 significantly decreased the expression level of Rab25 and other prominent apoptosis-related proteins in female A/J mice. The apoptosis in these mice was determined by detecting the expression level of Bcl-2, proliferating cell nuclear antigen, Bax, and further confirmed by TUNEL assay. Conclusions: Our results strongly confirm the tumorigenic role of Rab25 in tobacco carcinogen-induced lung cancer and hence demonstrate aerosol delivery of shRab25 as a therapeutic target for lung cancer treatment.
ISSN
1941-2711
URI
https://hdl.handle.net/10371/172411
DOI
https://doi.org/10.1089/jamp.2016.1301
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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