Radiosensitization by targeting radioresistance-related genes with protein kinase A inhibitor in radioresistant cancer cells.
- Author:
Chur CHIN
1
;
Jae Ho BAE
;
Mi Ju KIM
;
Jee Young HWANG
;
Su Jin KIM
;
Man Soo YOON
;
Min Ki LEE
;
Dong Wan KIM
;
Byung Seon CHUNG
;
Chi Dug KANG
;
Sun Hee KIM
Author Information
1. Department of Biochemistry, Pusan National University Hospital, Busan 602-739, Korea. ksh7738@pusan.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
cyclic AMP-dependent protein kinases;
gene expression profiling;
gene expression regulation, neoplastic;
radiation
- MeSH:
Animals;
Apoptosis/drug effects;
Cell Line, Tumor;
Cyclic AMP-Dependent Protein Kinases/*antagonists & inhibitors/metabolism;
DNA Damage/drug effects;
DNA Repair/drug effects;
Gamma Rays;
Gene Expression Regulation, Neoplastic/radiation effects;
Genes, bcl-2;
Humans;
Mice;
Neoplasm Proteins/genetics/metabolism;
Neoplasms/enzymology/*genetics;
Radiation Tolerance/*genetics;
Research Support, Non-U.S. Gov't
- From:Experimental & Molecular Medicine
2005;37(6):608-618
- CountryRepublic of Korea
- Language:English
-
Abstract:
Here we determined which radiation-responsive genes were altered in radioresistant CEM/IR and FM3A/IR variants, which showed higher resistance to irradiation than parental human leukemia CEM and mouse mammary carcinoma FM3A cells, respectively and studied if radioresistance observed after radiotherapy could be restored by inhibition of protein kinase A. The expressions of DNA-PKcs, Ku70/80, Rad51 and Rad54 genes that related to DNA damage repair, and Bcl-2 and NF-kappaB genes that related to antiapoptosis, were up-regulated, but the expression of proapototic Bax gene was down-regulated in the radioresistant cells as compared to each parental counterpart. We also revealed that the combined treatment of radiation and the inhibitor of protein kinase A (PKA) to these radioresistant cells resulted in synergistic inhibition of DNA-PK, Rad51 and Bcl-2 expressions of the cells, and consequently restored radiosensitivity of the cells. Our results propose that combined treatment with radiotherapy and PKA inhibitor can be a novel therapeutic strategy to radioresistant cancers.
