2. Academic Validation
  3. Disruption of protein neddylation with MLN4924 attenuates paclitaxel-induced apoptosis and microtubule polymerization in ovarian cancer cells

Disruption of protein neddylation with MLN4924 attenuates paclitaxel-induced apoptosis and microtubule polymerization in ovarian cancer cells

  • Biochem Biophys Res Commun. 2019 Jan 15;508(3):986-990. doi: 10.1016/j.bbrc.2018.12.048.
Xiaoling Hong 1,  Siying Li 2,  Wanying Li 2,  Min Xie 2,  Zhentong Wei 2,  Haoran Guo 3,  Wei Wei 4,  Songling Zhang 5
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun, Jilin 130021, China; Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin 130021, China.
  • 2 Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun, Jilin 130021, China.
  • 3 Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin 130021, China.
  • 4 Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin 130021, China. Electronic address: wwei6@jlu.edu.cn.
  • 5 Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun, Jilin 130021, China. Electronic address: slzhang@jlu.edu.cn.
PMID: 30545630 DOI: 10.1016/j.bbrc.2018.12.048
Abstract

Surgery and chemotherapy are the gold-standard treatments for ovarian Cancer. The major cause of treatment failure in patients with ovarian Cancer is tumoral heterogeneity and drug resistance. Paclitaxel (PTX) is one of the most commonly used first-line drugs for ovarian Cancer chemotherapy. Unfortunately, the mechanisms of PTX chemoresistance remain unclear. Here, we examined the effects of post-translational neddylation on the sensitivity of ovarian Cancer cells (OCCs) to PTX-induced Apoptosis. Disruption of protein neddylation with the first-in-class inhibitor MLN4924 dramatically neutralized PTX-mediated antiproliferative, antimigration, and apoptotic effects in human OCCs. Moreover, MLN4924 treatment interrupted PTX-induced microtubule polymerization. Importantly, two neddylation conjugating E2 Enzymes, UBE2M and UBE2F, were found to play essential roles in PTX-induced cytotoxicity and tubulin polymerization in OCCs. In summary, our findings demonstrated that disruption of protein neddylation by MLN4924 conferred resistance to PTX and provided insights into the potential mechanisms of PTX chemoresistance in ovarian Cancer.

Keywords

MLN4924; Neddylation; Ovarian cancer; Paclitaxel resistance.

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