Acquired Radioresistance Of Human Colon Cancer Cells By DNA-PK/AKT/GSK3β Path

Objective：To investigate the molecular mechanism of human colon cancercell line SW480which exposured to long-term fractionated radiation (FR)Methods：The level of cyclin D1mRNA in parental SW480cells and theradioresistant subline SW480-R which were selected by premier experimentwith long-term fractionated radiation after single irradiation with different dosesof0Gy、2Gy、5Gy、10Gy were detected by real-time fluorescent quantitativepoly-merase chain reaction(PCR).Using western blotting to detect theDNA-PK/AKT/GSK3β pathway of cyclin D1、AKT、p-AKT-Ser473、GSK3β、p-GSK3β-Ser9、DNA-PKcs、p-DNA-PKcs protein expression of SW480cellsand SW480-R cells after single irradiation with different doses of0Gy、2Gy、5Gy、10Gy.Results：After single irradiation with different doses of0Gy、2Gy、5Gy、10Gy, the cyclin D1mRNA expression level in the radioresistant sublineSW480-R was weaker than SW480cells（P＜0.05）.The relative expressionlevels were0.31±0.02,0.32±0.03,0.34±0.05and0.44±0.04. Western blottingrevealed that cyclin D1、AKT、p-AKT-Ser473、p-GSK3β-Ser9、DNA-PKcs and p-DNA-PKcs protein expression in SW480-R cells were higher than in SW480cell（sP＜0.05）after single irradiation with different doses of0Gy、2Gy、5Gy、10Gy. Conversely, the resistant SW480-R cells showed a lower level of GSK3βprotein expression than the parental SW480cells（P＜0.05）Conclusion：Human colon cancer cell line that acquired radioresistanceafter long-term FR was connected with alterations by cyclin D1overexpressionwhich attributed to activate the DNA-PK/AKT/GSK3β pathway.