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Downregulation of DNA-PKcs suppresses P-gp expression via inhibition of the Akt/NF-κB pathway in CD133-positive osteosarcoma MG-63 cells

  • Authors:
    • Ka Li
    • Xin Li
    • Jiguang Tian
    • Hongliang Wang
    • Jingbo Pan
    • Jianmin Li

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  • Published online on: August 2, 2016     https://doi.org/10.3892/or.2016.4991
  • Pages: 1973-1980
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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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October-2016
Volume 36 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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  • CiteScore: 8.5
  • CiteScore Rank: Q1: #74/404 Oncology
  • Source Normalized Impact per Paper (SNIP): 0.719
  • SCImago Journal Rank (SJR): 0.864
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Spandidos Publications style
Li K, Li X, Tian J, Wang H, Pan J and Li J: Downregulation of DNA-PKcs suppresses P-gp expression via inhibition of the Akt/NF-κB pathway in CD133-positive osteosarcoma MG-63 cells. Oncol Rep 36: 1973-1980, 2016.
APA
Li, K., Li, X., Tian, J., Wang, H., Pan, J., & Li, J. (2016). Downregulation of DNA-PKcs suppresses P-gp expression via inhibition of the Akt/NF-κB pathway in CD133-positive osteosarcoma MG-63 cells. Oncology Reports, 36, 1973-1980. https://doi.org/10.3892/or.2016.4991
MLA
Li, K., Li, X., Tian, J., Wang, H., Pan, J., Li, J."Downregulation of DNA-PKcs suppresses P-gp expression via inhibition of the Akt/NF-κB pathway in CD133-positive osteosarcoma MG-63 cells". Oncology Reports 36.4 (2016): 1973-1980.
Chicago
Li, K., Li, X., Tian, J., Wang, H., Pan, J., Li, J."Downregulation of DNA-PKcs suppresses P-gp expression via inhibition of the Akt/NF-κB pathway in CD133-positive osteosarcoma MG-63 cells". Oncology Reports 36, no. 4 (2016): 1973-1980. https://doi.org/10.3892/or.2016.4991