Open Access

Apurinic endonuclease 1 promotes the cisplatin resistance of lung cancer cells by inducing Parkin‑mediated mitophagy

  • Authors:
    • Zheng Li
    • Yongqiang Wang
    • Linbo Wu
    • Yalu Dong
    • Jing Zhang
    • Fan Chen
    • Wei Xie
    • Jianguo Huang
    • Ning Lu
  • View Affiliations

  • Published online on: October 1, 2019     https://doi.org/10.3892/or.2019.7345
  • Pages: 2245-2254
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Platinum‑containing doublet chemotherapy is the cornerstone of lung cancer treatment; however, cisplatin resistance is a major obstacle in the treatment of lung cancer. However, the mechanism underlying this resistance has not been fully elucidated. Previous studies have shown that serum apurinic/apyrimidinic endonuclease 1 (APE1) levels in patients with NSCLC are inversely associated with progression‑free survival after platinum‑containing doublet chemotherapy, and can serve as a biomarker for predicting disease prognosis and treatment efficacy. The present study was designed to investigate the role played by APE1 in the resistance of lung cancer to cisplatin. The levels of mitochondrial apurinic endonuclease 1 (m‑APE1) and total APE1 (t‑APE1) protein in a cisplatin‑resistant A549 cell line (A549/DDP) and cisplatin‑sensitive A549 cells were analyzed by western blotting. Mitochondrial membrane potential was detected by using the JC‑1 staining method. The cisplatin‑resistance of APE1‑overexpressing A549 cells and APE1‑silenced A549/DDP cells was assessed by cell apoptosis and colony formation assays. The results revealed that cisplatin‑resistant A549 cells contained high levels of APE1, and exhibited elevated levels of autophagy. The levels of m‑APE1 and t‑APE1 protein were increased in the A549/DDP cells when compared with these levels in the A549 cells. Overexpression of APE1 and Mia40 enhanced the cisplatin resistance and autophagy of the A549 cells. APE1 knockdown restored the cisplatin sensitivity and reduced the levels of LC3II and Parkin in the A549/DDP cells, but promoted the release of cytochrome c. Furthermore, Parkin silencing or treatment with 3‑methyladenine (3‑MA, an autophagy inhibitor) promoted the apoptosis of APE1‑overexpressing A549 cells, indicating that Parkin‑mediated mitophagy plays an important role in the APE1‑induced cisplatin resistance of A549 cells. In conclusion, APE1 promotes the cisplatin resistance of lung cancer cells by inducing Parkin‑mediated mitophagy.
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December-2019
Volume 42 Issue 6

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

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Copy and paste a formatted citation
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Spandidos Publications style
Li Z, Wang Y, Wu L, Dong Y, Zhang J, Chen F, Xie W, Huang J and Lu N: Apurinic endonuclease 1 promotes the cisplatin resistance of lung cancer cells by inducing Parkin‑mediated mitophagy. Oncol Rep 42: 2245-2254, 2019
APA
Li, Z., Wang, Y., Wu, L., Dong, Y., Zhang, J., Chen, F. ... Lu, N. (2019). Apurinic endonuclease 1 promotes the cisplatin resistance of lung cancer cells by inducing Parkin‑mediated mitophagy. Oncology Reports, 42, 2245-2254. https://doi.org/10.3892/or.2019.7345
MLA
Li, Z., Wang, Y., Wu, L., Dong, Y., Zhang, J., Chen, F., Xie, W., Huang, J., Lu, N."Apurinic endonuclease 1 promotes the cisplatin resistance of lung cancer cells by inducing Parkin‑mediated mitophagy". Oncology Reports 42.6 (2019): 2245-2254.
Chicago
Li, Z., Wang, Y., Wu, L., Dong, Y., Zhang, J., Chen, F., Xie, W., Huang, J., Lu, N."Apurinic endonuclease 1 promotes the cisplatin resistance of lung cancer cells by inducing Parkin‑mediated mitophagy". Oncology Reports 42, no. 6 (2019): 2245-2254. https://doi.org/10.3892/or.2019.7345