Open Access

Triptolide inhibits epithelial‑mesenchymal transition and induces apoptosis in gefitinib‑resistant lung cancer cells

  • Authors:
    • Fangqiong Li
    • Huaizhong Cui
    • Xin Jin
    • Xiaoting Gong
    • Wei Wang
    • Juan Wang
  • View Affiliations

  • Published online on: March 10, 2020     https://doi.org/10.3892/or.2020.7542
  • Pages: 1569-1579
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The epidermal growth factor receptor‑tyrosine kinase inhibitor (EGFR‑TKI), gefitinib, is used widely to treat non‑small cell lung cancer (NSCLC) with EGFR‑activating mutations. Unfortunately, the acquired drug resistance promoted by epithelial‑mesenchymal transition (EMT) markedly limits the clinical effects and remains a major barrier to a cure. Our previous isobaric tags for relative and absolute quantitation‑based proteomics analysis revealed that the E‑cadherin protein level was markedly upregulated by triptolide (TP). The present study aimed to determine whether TP reverses the gefitinib resistance of human lung cancer cells by regulating EMT. It was revealed that TP combined with gefitinib synergistically inhibited the migration and invasion of lung adenocarcinoma cell line A549; the combination treatment had a significantly better outcome than that of TP and gefitinib alone. Moreover, TP effectively increased the sensitivity of drug resistant A549 cells to gefitinib by upregulating E‑cadherin protein expression and downregulating the MMP9, SNAIL, and vimentin expression levels. The dysregulated E‑cadherin expression of gefitinib‑sensitive cells induced gefitinib resistance, which could be overcome by TP. Finally, TP combined with gefitinib significantly inhibited the growth of xenograft tumors induced using gefitinib‑resistant A549 cells, which was associated with EMT reversal and E‑cadherin signaling activation in vivo. The present results indicated that the combination of TP and TKIs may be a promising therapeutic strategy to treat patients with NSCLCs harboring EGFR mutations.

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May 2020
Volume 43 Issue 5

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

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APA
Li, F., Cui, H., Jin, X., Gong, X., Wang, W., & Wang, J. (2020). Triptolide inhibits epithelial‑mesenchymal transition and induces apoptosis in gefitinib‑resistant lung cancer cells. Oncology Reports, 43, 1569-1579. https://doi.org/10.3892/or.2020.7542
MLA
Li, F., Cui, H., Jin, X., Gong, X., Wang, W., Wang, J."Triptolide inhibits epithelial‑mesenchymal transition and induces apoptosis in gefitinib‑resistant lung cancer cells". Oncology Reports 43.5 (2020): 1569-1579.
Chicago
Li, F., Cui, H., Jin, X., Gong, X., Wang, W., Wang, J."Triptolide inhibits epithelial‑mesenchymal transition and induces apoptosis in gefitinib‑resistant lung cancer cells". Oncology Reports 43, no. 5 (2020): 1569-1579. https://doi.org/10.3892/or.2020.7542