Chemoresistance of multi-drug resistance malignant glioma cells mediated by DNA-PKcs and its molecular mechanism
10.13481/j.1671-587x.20160507
- VernacularTitle:DNA-PKcs 介导多药耐药恶性胶质瘤细胞化疗抗性及分子机制
- Author:
Shuang HUI
;
Hongqiang GUO
- Publication Type:Journal Article
- Keywords:
DNA-dependent kinase;
glioma;
chemoresistance;
multi drug resistance protein 1
- From:
Journal of Jilin University(Medicine Edition)
2016;42(5):877-881
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To obesrve the influence of DNA-PKcs in the chemoresistance of multi-drug resistance malignant glioma cells,and to explore its molecuIar mechanism in chemoresistance.Methods:siRNA was used to construct the DNA-PKcs knockdown human glioma U251 cell line;Western blotting method was used to detect the expressions of DNA-PKcs in U251 cells (U251 cells), doxorubicin (ADM)resistant U251 cells (U251/ADM cells),DNA-PKcs knockdown and ADM resistant U251 cells (U251/ADM/siDNA-PKcs cells).CCK8 method was used to detect the cell proliferation activity in three groups;Western blotting method was used to detect the expressions of MDR1, pNF-κB/p6, total Akt, pAkt/T308 and pAKT/S473 in the cells in three groups. Results:The expression level of DNA-PKcs in U251/ADM cells was significantly higher than those in U251 cells and U251/ADM/siDNA-PKcs cells (P < 0.01 ).The IC50 values of doxorubicin (ADM),paclitaxel (PTX), gemcitabine (GEM)in U251/ADM/siDNA-PKcs cells were significantly lower than that in U251/ADM cells (P <0.05);the expression levels of pAKT/S473,pNF-κB/p65,and MDR1 in U251/ADM/siDNA-PKcs cells were significantly lower than those in U251/ADM cells (P <0.01),but the total Akt and pAkt/T308 had no significant differences between two groups (P >0.05).Conclusion:DNA-PKcs can significantly enhance the chemoresistance of multi-drug resistance malignant glioma cells,the underlying mechanism is related to up-regulation of pAKT/S473,pNF-κB/p65 and MDR1 expressions.
