TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000649815
  • Gene Name:AKT
  • mRNA database:Ensembl
  • mRNA expression :up-regulated
  • mRNA Method:qPCR
  • mRNA Pathway:NA
  • Evidence:predicted
  • (mRNA-drug)

Drug basic information

  • Drug ID:NA
  • Drug Name:NA
  • Drug Method:NA

Disease basic infommation

  • Disease:osteosarcoma
  • Tissue:The human MG-63 cell line

Other information

  • Title:Downregulation of DNA-PKcs suppresses P-gp expression via inhibition of the Akt/NF-kBpathway in CD133-positive osteosarcoma MG-63 cells.
  • Journal:Oncol Rep
  • Published:2016
  • PubMed ID:27499034
  • Abstract:The development of chemoresistance is closely linked to the plateau of the survival rate in osteosarcoma (OS) patients. CD133-positive (CD133+) OS cells are known as cancer stem cells (CSCs) in OS and exhibit the characteristic of chemoresistance. In this study, CD133+ and CD133-negative (CD133-) MG-63 cells were isolated by magnetic activated cell sorting (MACS). We verified that CD133+ MG-63 cells were more resistant to cisplatin (CDDP) than CD133- MG-63 cells. DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and P-glycoprotein (P-gp) were expressed at higher levels in the CD133+ MG-63 cells compared with those levels in the CD133- MG-63 cells, whereas downregulation of DNA-PKcs by small interfering RNA (siRNA) decreased chemoresistance to CDDP and P-gp expression at the mRNA and protein levels in these cells. This indicated that DNA-PKcs was correlated with P-gp expression in the CD133+ MG-63 cells. The Akt/NF-κB pathway was hyperactivated in the CD133+ MG-63 cells, whereas inhibition of the Akt/NF-κB pathway downregulated P-gp expression. In addition, downregulation of DNA-PKcs suppressed the activity of the Akt/NF-κB pathway. These results revealed that downregulation of DNA-PKcs could decrease P-gp expression via suppression of the Akt/NF-κB pathway in CD133+ MG-63 cells. Therefore, inhibition of DNA-PKcs decreases P-gp expression and sensitizes OS CSCs to chemotherapeutic agents in vitro, which needs to be further validated in vivo.
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