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Aerosol delivery of beclin1 enhanced the anti-tumor effect of radiation in the lungs of K-ras(LA1) mice

Cited 12 time in Web of Science Cited 12 time in Scopus
Authors
Shin, Ji-Young; Lim, Hwang-Tae; Minai-Tehrani, Arash; Noh, Mi-Suk; Kim, Ji-Eun; Kim, Ji-Hye; Jiang, Hu-Lin; Arote, Rohidas; Kim, Doo-Yeol; Chae, Chanhee; Lee, Kee-Ho; Kim, Mi-Sook; Cho, Myung-Haing
Issue Date
2012-07
Citation
Journal of Radiation Research, Vol.53 No.4, pp.506-515
Keywords
RadiationBeclin 1aerosol deliverylung cancer
Abstract
Radiotherapy alone has several limitations for treating lung cancer. Inhalation, a non-invasive approach for direct delivery of therapeutic agents to the lung, may help to enhance the therapeutic efficacy of radiation. Up-regulating beclin 1, known as a tumor suppressor gene that plays a major role in autophagy, may sensitize tumors and lead to tumor regression in lungs of K-ras(LA1) lung cancer model mice. To minimize the side-effects of radiotherapy, fractionated exposures (five times, 24-h interval) with low dose (2 Gy) of radiation to the restricted area (thorax, 2 cm) were conducted. After sensitizing the lungs with radiation, beclin 1, complexed with a nano-sized biodegradable poly(ester amine), was prepared and delivered into the murine lung via aerosol three times/week for four weeks. In a histopathological analysis, animals treated with beclinl and radiation showed highly significant tumor regression and low progression to adenocarcinoma. An increase in the number of autophagic vacuoles and secondary lysosomes was detected. Dissociation of beclin 1-bcl2 stimulated autophagy activation and showed a synergistic anti-tumor effect by inhibiting the Akt-mTOR pathway, cell proliferation and angiogenesis. The combination of radiation with non-invasive aerosol delivery of beclinl may provide a prospect for developing novel therapy regimens applicable in clinics.
ISSN
0449-3060
URI
https://hdl.handle.net/10371/172446
DOI
https://doi.org/10.1093/jrr/rrs005
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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