title: Radiosensitization by targeting radioresistance-related genes with protein kinase A inhibitor in radioresistant cancer cells.
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.
authors.affiliation: Department of Biochemistry, Pusan National University Hospital, Busan 602-739, Korea.
authors.forename: Chur
authors.initials: C
authors.lastname: Chin
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Bae
authors.forename: Mi Ju
authors.initials: MJ
authors.lastname: Kim
authors.forename: Jee Young
authors.initials: JY
authors.lastname: Hwang
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Man Soo
authors.initials: MS
authors.lastname: Yoon
authors.forename: Min Ki
authors.initials: MK
authors.lastname: Lee
authors.forename: Dong Wan
authors.initials: DW
authors.lastname: Kim
authors.forename: Byung Seon
authors.initials: BS
authors.lastname: Chung
authors.forename: Chi Dug
authors.initials: CD
authors.lastname: Kang
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D019254:Genes, bcl-2; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics*
chemical_list: D009363:Neoplasm Proteins; D017868:Cyclic AMP-Dependent Protein Kinases