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

  • Published online on: November 1, 2017     https://doi.org/10.3892/ol.2017.7314
  • Pages:515-521
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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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January 2018
Volume 15 Issue 1

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

2016 Impact Factor: 1.39
Ranked #68/217 Oncology
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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