Open Access

Activity and mechanism of flavokawain A in inhibiting permeability P‑glycoprotein expression in paclitaxel resistance of lung cancer

  • Authors:
    • Juan Li
    • Lei Zheng
    • Mi Yan
    • Jing Wu
    • Yongqing Liu
    • Xiaona Tian
    • Wen Jiang
    • Lu Zhang
    • Rongmei Wang
  • View Affiliations

  • Published online on: November 8, 2019     https://doi.org/10.3892/ol.2019.11069
  • Pages: 379-387
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Lung cancer is one of the most common cancers, which is the leading cause of cancer‑related death among various cancers worldwide. Flavokawain A (FKA), a chalcone found in the kava plant, exerts potent anticancer activity. However, the activity and mechanisms of FKA in inhibiting the viability of paclitaxel (PTX)‑resistant lung cancer A549 (A549/T) have not been investigated. In the present study, the effect of FKA on the viability of A549/T and hepatotoxicity in normal liver epithelial cells was detected by Cell Counting Kit‑8 assay. Flow cytometry, western blot analysis and Annexin V‑FITC/PI apoptosis detection kit were used to assess cell apoptosis. The effect of FKA on permeability‑glycoprotein (P‑gp) expression was measured by reverse transcription‑PCR and western blot analysis. The results indicated that FKA dose‑dependently inhibited cell proliferation and induced cell apoptosis in PTX‑resistant A549/T cells, with an IC50 value of ~21 µM, while the IC50 value of A549/T cells to PTX was 34.64 µM. FKA had no hepatic toxicity in liver epithelial cells. P‑gp, which contributes to the chemoresistant phenotype, was not expressed in A549 cells but was remarkably enhanced in A549/T cells. FKA (30 µM) decreased P‑gp protein expression at 24 h by 3‑fold. Furthermore, FKA downregulated P‑gp expression by blocking the PI3K/Akt pathway. These findings suggest FKA as a potential candidate for the treatment of PTX‑resistant lung cancer.
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January-2020
Volume 19 Issue 1

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Li J, Zheng L, Yan M, Wu J, Liu Y, Tian X, Jiang W, Zhang L and Wang R: Activity and mechanism of flavokawain A in inhibiting permeability P‑glycoprotein expression in paclitaxel resistance of lung cancer. Oncol Lett 19: 379-387, 2020.
APA
Li, J., Zheng, L., Yan, M., Wu, J., Liu, Y., Tian, X. ... Wang, R. (2020). Activity and mechanism of flavokawain A in inhibiting permeability P‑glycoprotein expression in paclitaxel resistance of lung cancer. Oncology Letters, 19, 379-387. https://doi.org/10.3892/ol.2019.11069
MLA
Li, J., Zheng, L., Yan, M., Wu, J., Liu, Y., Tian, X., Jiang, W., Zhang, L., Wang, R."Activity and mechanism of flavokawain A in inhibiting permeability P‑glycoprotein expression in paclitaxel resistance of lung cancer". Oncology Letters 19.1 (2020): 379-387.
Chicago
Li, J., Zheng, L., Yan, M., Wu, J., Liu, Y., Tian, X., Jiang, W., Zhang, L., Wang, R."Activity and mechanism of flavokawain A in inhibiting permeability P‑glycoprotein expression in paclitaxel resistance of lung cancer". Oncology Letters 19, no. 1 (2020): 379-387. https://doi.org/10.3892/ol.2019.11069