Open Access

Erastin/sorafenib induces cisplatin‑resistant non‑small cell lung cancer cell ferroptosis through inhibition of the Nrf2/xCT pathway

  • Authors:
    • Yu Li
    • Hengyi Yan
    • Xiaoman Xu
    • Hongbo Liu
    • Cen Wu
    • Li Zhao
  • View Affiliations

  • Published online on: November 7, 2019     https://doi.org/10.3892/ol.2019.11066
  • Pages: 323-333
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Non‑small cell lung cancer (NSCLC) has long been one of the most lethal types of cancer due to its lack of typical clinical symptoms at early stages and high risk of tumour recurrence, even following complete surgical resection. Multicourse chemotherapy based on cisplatin (CDDP) is the standard adjuvant treatment for NSCLC; however, its benefits for the overall survival of patients are limited. In this study, NSCLC cells possessing CDDP‑resistant characteristics (N5CP cells), obtained from surgical resection of clinical specimens of patients with NSCLC, were cultured and screened to generate research models. This study aimed to identify the mechanism underlying tumour cell resistance to CDDP and to identify a novel treatment for NSCLC following CDDP failure. CDDP‑mediated NF‑E2 related factor 2 (Nrf2)/light chain of System xc‑ (xCT) pathway activation was associated with the resistance of cells to CDDP. Therefore, erastin/sorafenib regulation of Nrf2 or xCT expression may alter the sensitivity of tumour cells to CDDP. The small molecules erastin and sorafenib effectively induced N5CP cell ferroptosis, which was mediated by the accumulation of intracellular lipid reactive oxygen species. Additionally, low doses of erastin or sorafenib could be used in association with CDDP to effectively trigger N5CP cell ferroptosis. Furthermore, it was indicated that erastin and sorafenib, alone or in combination with a low dose of CDDP, effectively inhibited the growth of N5CP cells in vivo. Therefore, ferroptosis inducers, including erastin and sorafenib, may be considered a novel treatment regimen for patients with NSCLC, particularly patients with CDDP failure.
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January 2020
Volume 19 Issue 1

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

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APA
Li, Y., Yan, H., Xu, X., Liu, H., Wu, C., & Zhao, L. (2020). Erastin/sorafenib induces cisplatin‑resistant non‑small cell lung cancer cell ferroptosis through inhibition of the Nrf2/xCT pathway. Oncology Letters, 19, 323-333. https://doi.org/10.3892/ol.2019.11066
MLA
Li, Y., Yan, H., Xu, X., Liu, H., Wu, C., Zhao, L."Erastin/sorafenib induces cisplatin‑resistant non‑small cell lung cancer cell ferroptosis through inhibition of the Nrf2/xCT pathway". Oncology Letters 19.1 (2020): 323-333.
Chicago
Li, Y., Yan, H., Xu, X., Liu, H., Wu, C., Zhao, L."Erastin/sorafenib induces cisplatin‑resistant non‑small cell lung cancer cell ferroptosis through inhibition of the Nrf2/xCT pathway". Oncology Letters 19, no. 1 (2020): 323-333. https://doi.org/10.3892/ol.2019.11066