Journal of Jilin University Medicine Edition ›› 2016, Vol. 42 ›› Issue (05): 877-881.doi: 10.13481/j.1671-587x.20160507

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Chemoresistance of multi-drug resistance malignant glioma cells mediated by DNA-PKcs and its molecular mechanism

HUI Shuang, GUO Hongqiang   

  1. Department of Oncology, Nanyang Central Hospital, Henan Province, Nanyang 473009, China
  • Received:2016-04-19 Online:2016-09-28 Published:2016-09-29

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.

Key words: DNA-dependent kinase, glioma, chemoresistance, multi drug resistance protein 1

CLC Number: 

  • R739.4