Zinc Oxide Nanoparticles Inhibit Malignant Progression and Chemotherapy Resistance of Ovarian Cancer Cells by Activating Endoplasmic Reticulum Stress and Promoting Autophagy
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The mortality rate of ovarian cancer (OC) is high, posing a serious threat to women's lives. Zinc oxide nanoparticles (ZnO-NPs) show great potential in the treatment of cancer. However, the mechanism of ZnO-NPs in inhibiting the malignant proliferation and chemotherapy resistance of OC has remained elusive. In the present study, ZnO-NPs at different concentrations were used to treat SKOV3 cells, and subsequently, analyses including the Cell Counting Kit-8 assay, EDU staining, colony-formation assay, flow cytometry, wound-healing assay, Transwell assay and western blot were used to detect cell proliferation, invasion, migration, epithelial-mesenchymal transition (EMT) and chemotherapy resistance, as well as endoplasmic reticulum stress (ERS)- and autophagy-related indicators. Finally, the mechanisms of action of ZnO-NPs on OC were examined by adding ERS inhibitor 4-phenylbutyric acid (4-PBA) and autophagy inhibitor 3-methyladenine (3-MA). It was found that ZnO-NPs inhibited SKOV3 cell proliferation, facilitated apoptosis and induced cell cycle arrest. Furthermore, ZnO-NPs inhibited the invasion, migration and EMT of SKOV3 cells. ZnO-NPs also inhibited chemotherapy resistance of SKOV3 cells. ZnO-NPs activated ERS and promoted autophagy. The addition of 4-PBA or 3-MA significantly reversed the effects of ZnO-NPs on SKOV3 cells. Overall, ZnO-NPs inhibit the malignant progression and the chemotherapy resistance of SKOV3 cells by activating ERS and promoting autophagy.
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