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Blockade of NF-kappa B activation by I kappa B alpha gene therapy enhances radiation sensitivity and abolishes acquired resistance to radiation

Cited 3 time in Web of Science Cited 3 time in Scopus
Authors
Lee, Choon-Taek; Park, Mi Young; Kim, Dal Rae; Choi, Eun Kyung; Kim, Young Whan; Shim, Young-Soo; Kim, Yeon-Soo; Han, Sung Koo; Yoo, Chul-Gyu
Issue Date
2009-06
Publisher
SPANDIDOS PUBL LTD
Citation
MOLECULAR MEDICINE REPORTS; Vol.2 3; 471-475
Keywords
nuclear factor-kappa Badenovirus-I kappa B alpharadioresistancelung cancer
Abstract
Radiation is one of the main treatment modalities in lung cancer, but low sensitivity and acquired resistance of lung cancer cells to radiation frequently result in treatment failure. The activation of nuclear factor (NF)-kappa B is reportedly the main mechanism by which cancer cells exhibit resistance to external stresses, such as chemotherapy or radiation therapy. In this study, we blocked the activation of NF-kappa B by adenovirus-expressing I kappa B alpha-SR and investigated the effect this had on radiation sensitivity. Transduction with ad-I kappa B alpha effectively blocked the activation of NF-kappa B by radiation in all the cancer cell lines tested, except for NCI H460. Clonogenic assay after radiation demonstrated that ad-I kappa B alpha transduction enhanced the sensitivity to radiation of the lung cancer cell lines and HeLa cells, except for NCT H460. The radiosensitizing effect of I kappa B alpha was more potent in lung cancer cell lines with radioresistance (SKMESres) (sensitizer enhancement ratio 1:6 1). From these findings, NF-kappa B blockade by ad-I kappa B alpha enhanced the radiation sensitivity and also abolished the acquired radiation resistance of lung cancer cell lines. This study provides a therapeutic rationale for combining an NF-kappa B-blocking strategy with radiation to both increase sensitivity and overcome acquired resistance to radiation.
ISSN
1791-2997
Language
English
URI
http://hdl.handle.net/10371/77412
DOI
https://doi.org/10.3892/mmr_00000123
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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