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Article

MLN4924 neddylation inhibitor promotes cell death in paclitaxel‑resistant human lung adenocarcinoma cells

  • Authors:
    • Qiang Xu
    • Guibin Lin
    • Huizhe Xu
    • Lulu Hu
    • Yupeng Wang
    • Sha Du
    • Wuguo Deng
    • Wenxian Hu
    • Wei Cheng
    • Ke Jiang
  • View Affiliations / Copyright

    Affiliations: Department of Orthopedics, The Affiliated Yuhuangding Hospital of Qingdao University Medical College, Yantai, Shandong 264000, P.R. China, Institute of Cancer Stem Cell, Dalian Medical University Cancer Center, Dalian, Liaoning 116044, P.R. China, Key Laboratory of Biotherapy of Zhejiang Province, Department of Surgical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310020, P.R. China
  • Pages: 515-521
    |
    Published online on: November 1, 2017
       https://doi.org/10.3892/ol.2017.7314
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Abstract

Acquired resistance to first‑line chemotherapeutics, including paclitaxel (PTX), is a primary factor contributing to chemotherapy failure in non‑small cell lung cancer (NSCLC) patients. Previous studies have identified that targeting NEDD8‑activating enzyme (NAE) with MLN4924 effectively overcomes platinum resistance in preclinical models of ovarian cancer. However, the underlying mechanisms are yet to be fully elucidated. The present study demonstrates that the inhibition of the neddylation pathway with MLN4924 an NAE inhibitor inhibited protein neddylation, inactivated cullin‑RING E3 ligase and exhibited a potent antiproliferative effect on PTX‑resistant A549 and H460 cells (A549/PTX and H460/PTX). The application of MLN4924 promotes apoptosis and DNA damage in A549/PTX and H460/PTX cells. Additionally, MLN4924 abrogated the 3‑dimensional growth potential of these cells and inhibited the formation of the A549/PTX and H460/PTX spheroids. Notably, combining MLN4924 with PTX did not exhibit synergy in PTX‑resistant NSCLC cells. Taken together, the results of the current study suggest that MLN4924 may be utilized as an effective strategy for the treatment of PTX‑resistant NSCLC.
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Copy and paste a formatted citation
Spandidos Publications style
Xu Q, Lin G, Xu H, Hu L, Wang Y, Du S, Deng W, Hu W, Cheng W, Jiang K, Jiang K, et al: MLN4924 neddylation inhibitor promotes cell death in paclitaxel‑resistant human lung adenocarcinoma cells. Oncol Lett 15: 515-521, 2018.
APA
Xu, Q., Lin, G., Xu, H., Hu, L., Wang, Y., Du, S. ... Jiang, K. (2018). MLN4924 neddylation inhibitor promotes cell death in paclitaxel‑resistant human lung adenocarcinoma cells. Oncology Letters, 15, 515-521. https://doi.org/10.3892/ol.2017.7314
MLA
Xu, Q., Lin, G., Xu, H., Hu, L., Wang, Y., Du, S., Deng, W., Hu, W., Cheng, W., Jiang, K."MLN4924 neddylation inhibitor promotes cell death in paclitaxel‑resistant human lung adenocarcinoma cells". Oncology Letters 15.1 (2018): 515-521.
Chicago
Xu, Q., Lin, G., Xu, H., Hu, L., Wang, Y., Du, S., Deng, W., Hu, W., Cheng, W., Jiang, K."MLN4924 neddylation inhibitor promotes cell death in paclitaxel‑resistant human lung adenocarcinoma cells". Oncology Letters 15, no. 1 (2018): 515-521. https://doi.org/10.3892/ol.2017.7314
Copy and paste a formatted citation
x
Spandidos Publications style
Xu Q, Lin G, Xu H, Hu L, Wang Y, Du S, Deng W, Hu W, Cheng W, Jiang K, Jiang K, et al: MLN4924 neddylation inhibitor promotes cell death in paclitaxel‑resistant human lung adenocarcinoma cells. Oncol Lett 15: 515-521, 2018.
APA
Xu, Q., Lin, G., Xu, H., Hu, L., Wang, Y., Du, S. ... Jiang, K. (2018). MLN4924 neddylation inhibitor promotes cell death in paclitaxel‑resistant human lung adenocarcinoma cells. Oncology Letters, 15, 515-521. https://doi.org/10.3892/ol.2017.7314
MLA
Xu, Q., Lin, G., Xu, H., Hu, L., Wang, Y., Du, S., Deng, W., Hu, W., Cheng, W., Jiang, K."MLN4924 neddylation inhibitor promotes cell death in paclitaxel‑resistant human lung adenocarcinoma cells". Oncology Letters 15.1 (2018): 515-521.
Chicago
Xu, Q., Lin, G., Xu, H., Hu, L., Wang, Y., Du, S., Deng, W., Hu, W., Cheng, W., Jiang, K."MLN4924 neddylation inhibitor promotes cell death in paclitaxel‑resistant human lung adenocarcinoma cells". Oncology Letters 15, no. 1 (2018): 515-521. https://doi.org/10.3892/ol.2017.7314
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