Low dose of arsenic trioxide inhibits multidrug resistant-related P-glycoprotein expression in human neuroblastoma cell line

  • Authors:
    • Ling Liu
    • Yang Li
    • Xilin Xiong
    • Kai Qi
    • Chi Zhang
    • Jianpei Fang
    • Haixia Guo
  • View Affiliations

  • Published online on: November 3, 2016     https://doi.org/10.3892/ijo.2016.3756
  • Pages: 2319-2330
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Abstract

This study investigated arsenic trioxide (As2O3), cisplatin (DDP) and etoposide (Vp16) on the anticancer effects and P-glycoprotein (P-gp) expression in neuroblastoma (NB) SK-N-SH cells. The potential influence of As2O3, DDP and Vp16 currently included in NB routine treatment protocols on cytotoxicity in SK-N-SH cells was measured by flow cytometry and drug half-maximal inhibitory concentration (IC50) was established. Moreover, chemotherapeutic agent-mediated changes of cellular expression levels of resistant-related P-gp, was monitored using western blotting. The data showed that As2O3, DDP and Vp16 significantly inhibited the growth and survival of the SK-N-SH cells at different concentration. Notably, the levels of apoptosis were upregulated in SK-N-SH cells with an acceleration of the exposure time and the concentration of As2O3, DDP and Vp16. As2O3, DDP and Vp16 were observed with their IC50 values on SK-N-SH cells being 3 µM, 8 and 100 µg/ml, respectively. Flow cytometry analysis showed that As2O3 at low concentrations in SK-N-SH cells led to enhanced accumulation of cell populations in G2/M phase with increasing the exposure time, and increased levels of apoptosis. In contrast, we observed that SK-N-SH cell populations arrested in S phase by DDP and Vp16. In vitro examination revealed that following pretreatment of SK-N-SH cells with As2O3, the expression of P-gp was not increased. The expression of P-gp downregulation were noted following the group treated by As2O3 at 2 and 3 µM. Exposed to As2O3 at 3 µM for 72 h, SK-N-SH cells exhibited lower expression of P-gp than 2 µM As2O3 for 72 h. In contrast, the expression of P-gp was upregulated by DDP and VP16. In summary, SK-N-SH cells were responsive to chemotherapeutic agent-induced apoptosis in a dose-dependent and time-dependent manner. In particular, ours findings showed that low dose of As2O3 markedly reduced the P-gp expression and increased apoptotic cell death in human NB cell line.
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December-2016
Volume 49 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Liu L, Li Y, Xiong X, Qi K, Zhang C, Fang J and Guo H: Low dose of arsenic trioxide inhibits multidrug resistant-related P-glycoprotein expression in human neuroblastoma cell line. Int J Oncol 49: 2319-2330, 2016.
APA
Liu, L., Li, Y., Xiong, X., Qi, K., Zhang, C., Fang, J., & Guo, H. (2016). Low dose of arsenic trioxide inhibits multidrug resistant-related P-glycoprotein expression in human neuroblastoma cell line. International Journal of Oncology, 49, 2319-2330. https://doi.org/10.3892/ijo.2016.3756
MLA
Liu, L., Li, Y., Xiong, X., Qi, K., Zhang, C., Fang, J., Guo, H."Low dose of arsenic trioxide inhibits multidrug resistant-related P-glycoprotein expression in human neuroblastoma cell line". International Journal of Oncology 49.6 (2016): 2319-2330.
Chicago
Liu, L., Li, Y., Xiong, X., Qi, K., Zhang, C., Fang, J., Guo, H."Low dose of arsenic trioxide inhibits multidrug resistant-related P-glycoprotein expression in human neuroblastoma cell line". International Journal of Oncology 49, no. 6 (2016): 2319-2330. https://doi.org/10.3892/ijo.2016.3756