Tetrandrine prevents multidrug resistance in the osteosarcoma cell line, U-2OS, by preventing Pgp overexpression through the inhibition of NF-κB signaling

  • Authors:
    • Yandong Lu
    • Fangguo Li
    • Tao Xu
    • Jie Sun
  • View Affiliations

  • Published online on: February 17, 2017     https://doi.org/10.3892/ijmm.2017.2895
  • Pages: 993-1000
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The development of multidrug resistance (MDR) remains a major limitation to successful chemotherapy in osteosarcoma. Preventing the introduction of MDR has been a research hotspot in clinical and investigational oncology. The aim of this study was to evaluate the preventive effects of tetrandrine (TET) against MDR in osteosarcoma. For this purpose, U-2OS human osteosarcoma cells were treated with paclitaxel alone or a combination of paclitaxel with TET. The cells treated with paclitaxel alone eventually acquired MDR along with the overexpression of and highly activated P-glycoprotein (Pgp), while the cells treated with the paclitaxel-TET combination were sensitive to chemotherapeutic drugs and expressed decreased levels of Pgp and less Pgp activity. The promoter activities of MDR gene 1 (MDR1) and nuclear factor (NF)‑κB, and the expression levels of NF-κB and p-IκB-α were all enhanced in the cells cultured with paclitaxel alone. NF-κB DNA-binding activity and the binding ability of NF-κB to the MDR1 promoter were also enhanced in the cells cultured with paclitaxel alone compared to the control cells. However, the expression and activity of NF-κB were significantly decreased in the paclitaxel-TET combination-treated group as compared with the cells treated with paclitaxel alone. On the whole, our findings suggest that TET prevents paclitaxel-induced MDR by inhibiting Pgp overexpression through a mechanism that may involve the inhibition of NF-κB signaling in osteosarcoma.
View Figures
View References

Related Articles

Journal Cover

April-2017
Volume 39 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Lu Y, Li F, Xu T and Sun J: Tetrandrine prevents multidrug resistance in the osteosarcoma cell line, U-2OS, by preventing Pgp overexpression through the inhibition of NF-κB signaling. Int J Mol Med 39: 993-1000, 2017
APA
Lu, Y., Li, F., Xu, T., & Sun, J. (2017). Tetrandrine prevents multidrug resistance in the osteosarcoma cell line, U-2OS, by preventing Pgp overexpression through the inhibition of NF-κB signaling. International Journal of Molecular Medicine, 39, 993-1000. https://doi.org/10.3892/ijmm.2017.2895
MLA
Lu, Y., Li, F., Xu, T., Sun, J."Tetrandrine prevents multidrug resistance in the osteosarcoma cell line, U-2OS, by preventing Pgp overexpression through the inhibition of NF-κB signaling". International Journal of Molecular Medicine 39.4 (2017): 993-1000.
Chicago
Lu, Y., Li, F., Xu, T., Sun, J."Tetrandrine prevents multidrug resistance in the osteosarcoma cell line, U-2OS, by preventing Pgp overexpression through the inhibition of NF-κB signaling". International Journal of Molecular Medicine 39, no. 4 (2017): 993-1000. https://doi.org/10.3892/ijmm.2017.2895