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Article

WWOX promotes apoptosis and inhibits autophagy in paclitaxel‑treated ovarian carcinoma cells

  • Authors:
    • Yan Zhao
    • Wen Wang
    • Wenying Pan
    • Yunhai Yu
    • Wenqian Huang
    • Jiangang Gao
    • Ying Zhang
    • Shiqian Zhang
  • View Affiliations / Copyright

    Affiliations: School of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China, Department of Gynecology and Obstetrics, Tengzhou Central People's Hospital, Zaozhuang, Shandong 277500, P.R. China, Department of Gynecology and Obstetrics, The Affiliated Hospital of Binzhou Medical College, Binzhou, Shandong 264003, P.R. China, Department of Gynecology and Obstetrics, The Second Hospital of Shandong University, Jinan, Shandong 250032, P.R. China, School of Life Sciences, Shandong University, Jinan, Shandong 250100, P.R. China, Department of Gynecology and Obstetrics, The First People's Hospital of Jining, Jining, Shandong 272000, P.R. China, Department of Gynecology and Obstetrics, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China
  • Article Number: 115
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    Published online on: December 3, 2020
       https://doi.org/10.3892/mmr.2020.11754
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Abstract

Although paclitaxel (PTX) is a first‑line chemotherapeutic agent for the treatment of epithelial ovarian cancer (EOC), its clinical use is restricted by chemoresistance. Autophagy is believed to promote drug resistance, and WW domain‑containing oxidoreductase (WWOX) has been predicted to serve an essential role in apoptosis induction and to suppress autophagy in various tumor cell types. In the present study, the role of WWOX was demonstrated using PTX‑treated EOC cells. Cell viability and apoptosis were detected using Cell Counting Kit‑8, morphological and flow cytometric analyses. WWOX and phosphorylated (p)‑WWOX were highly expressed in PTX‑treated sensitive EOC cells (A2780), which was accompanied by activation of the apoptosis‑related proteins caspase‑3 and poly (ADP‑ribose) polymerase (PARP). Conversely, PTX‑resistant EOC cells (A2780/T) were characterized by reduced WWOX expression and constant phosphorylation levels, as well as undetectable levels of activated caspase‑3 and PARP when cells were treated with PTX. The altered expression of WWOX between the two cell types was further validated by reverse transcription‑­quantitative PCR. The apoptosis‑inducing role of WWOX was also confirmed by flow cytometry after WWOX overexpression was induced in PTX‑treated A2780 cells. These findings indicated that WWOX activation may inhibit chemoresistance and trigger cancer cell death. The upregulated expression levels of the autophagy‑related protein 12‑5 complex, Beclin‑1 and LC3, as well as the downregulation of P62, were also detected following PTX treatment, suggesting that PTX induced autophagic flux in both types of EOC cells. This conclusion was further supported by visualizing the accumulation of autophagosome and autolysosome vesicles, using confocal microscopy and transmission electron microscopy. PTX was also shown to inhibit mTOR signaling, indicated by a decreased level of p‑mTOR and increased expression of eukaryotic translation initiation factor 4E‑binding protein 1. Finally, the interaction between WWOX, mTOR and autophagy was investigated via WWOX transfection experimentation, and indicated that WWOX activated mTOR whilst inhibiting autophagy. These data indicated that WWOX may serve a critical role in PTX‑induced apoptosis and could suppress autophagy by downregulating essential autophagic effectors in EOC cells via mTOR signaling.
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Copy and paste a formatted citation
Spandidos Publications style
Zhao Y, Wang W, Pan W, Yu Y, Huang W, Gao J, Zhang Y and Zhang S: WWOX promotes apoptosis and inhibits autophagy in paclitaxel‑treated ovarian carcinoma cells. Mol Med Rep 23: 115, 2021.
APA
Zhao, Y., Wang, W., Pan, W., Yu, Y., Huang, W., Gao, J. ... Zhang, S. (2021). WWOX promotes apoptosis and inhibits autophagy in paclitaxel‑treated ovarian carcinoma cells. Molecular Medicine Reports, 23, 115. https://doi.org/10.3892/mmr.2020.11754
MLA
Zhao, Y., Wang, W., Pan, W., Yu, Y., Huang, W., Gao, J., Zhang, Y., Zhang, S."WWOX promotes apoptosis and inhibits autophagy in paclitaxel‑treated ovarian carcinoma cells". Molecular Medicine Reports 23.2 (2021): 115.
Chicago
Zhao, Y., Wang, W., Pan, W., Yu, Y., Huang, W., Gao, J., Zhang, Y., Zhang, S."WWOX promotes apoptosis and inhibits autophagy in paclitaxel‑treated ovarian carcinoma cells". Molecular Medicine Reports 23, no. 2 (2021): 115. https://doi.org/10.3892/mmr.2020.11754
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao Y, Wang W, Pan W, Yu Y, Huang W, Gao J, Zhang Y and Zhang S: WWOX promotes apoptosis and inhibits autophagy in paclitaxel‑treated ovarian carcinoma cells. Mol Med Rep 23: 115, 2021.
APA
Zhao, Y., Wang, W., Pan, W., Yu, Y., Huang, W., Gao, J. ... Zhang, S. (2021). WWOX promotes apoptosis and inhibits autophagy in paclitaxel‑treated ovarian carcinoma cells. Molecular Medicine Reports, 23, 115. https://doi.org/10.3892/mmr.2020.11754
MLA
Zhao, Y., Wang, W., Pan, W., Yu, Y., Huang, W., Gao, J., Zhang, Y., Zhang, S."WWOX promotes apoptosis and inhibits autophagy in paclitaxel‑treated ovarian carcinoma cells". Molecular Medicine Reports 23.2 (2021): 115.
Chicago
Zhao, Y., Wang, W., Pan, W., Yu, Y., Huang, W., Gao, J., Zhang, Y., Zhang, S."WWOX promotes apoptosis and inhibits autophagy in paclitaxel‑treated ovarian carcinoma cells". Molecular Medicine Reports 23, no. 2 (2021): 115. https://doi.org/10.3892/mmr.2020.11754
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