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: Friday, February 17, 2017
  • DOI: 10.3892/ijmm.2017.2895
0

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.

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APA
Lu, Y., Li, F., Xu, T., & Sun, J. (1899). 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, 0, 0-0. http://dx.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 0.0 (1899): 0-0.
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 0, no. 0 (1899): 0-0. http://dx.doi.org/10.3892/ijmm.2017.2895