中国癌症防治杂志Issue(4)：296-299,4.DOI:10.3969/j.issn.1674-5671.2013.04.02
DNA-PK/AKT/GSK3β通路与结肠癌细胞的放射抗拒性
The DNA-PK/AKT/GSK3β pathway and acquired radioresistance in human colon cancer cells
摘要
Abstract
Objective To investigate the molecular mechanism of radioresistance acquisition after long-term fractionated radiation (FR)in human colon cancer cell line SW480. Methods Parental SW480 cells and radioresistant subline SW480-R cells were irradiated with single doses of 0,2,5 or 10 Gy.CCND1 mRNA levels were measured using real-time fluorescent quantitative polymerase chain reaction(PCR).Western blotting was used to measure levels of proteins involved in the DNA-PK/AKT/GSK3βpathway of SW480 cells and SW480-R cells,including cyclin D1,CDK4,Rb,p-Rb-Sebr795,AKT,p-AKT-Ser473,GSK3β,p-GSK3β-Ser9,DNA-PKcs and p-DNA-PKcs. Results CCND1 mRNA levels were significantly lower in the radioresistant subline SW480-R than in parental SW480 cells after single irradiation doses(P<0.05),with relative expression being 0.31±0.02 in the resistant subline compared to the parental line after 0 Gy,0.32±0.03 after 2 Gy,0.34±0.05 after 5 Gy and 0.44±0.04 after 10 Gy.Conversely levels of all proteins examined were higher in SW480-R cells than in SW480 cells(P<0.05)except the level of GSK3β,which was lower in SW480-R cells(P<0.05). Conclusions Acquired radioresistance in the human colon cancer cell line was correlated with alterations in the DNA damage response;these alterations were activated by long-term FR and mediated by cyclin D1 overexpression in the DNA-PK/AKT/GSK3βpathway.关键词
结肠肿瘤/cyclin D1/分割放疗/放射抗拒性/实时荧光定量聚合酶链式反应/Western blot法Key words
Colon neoplasms/Cyclin D1/Fractionated-radiation/Radioresistance/Real-time fluorescent quantitative polymerase chain reaction/Western blot分类
医药卫生引用本文复制引用
肖胜英,葛莲英,刘爱群,孙明辉..DNA-PK/AKT/GSK3β通路与结肠癌细胞的放射抗拒性[J].中国癌症防治杂志,2013,(4):296-299,4.基金项目
广西自然科学基金资助项目（2011GXSFA018205）；广西医疗卫生重点科研课题 （）
