Nigericin inhibits epithelial ovarian cancer metastasis by suppressing the cell cycle and epithelial−mesenchymal transition
Epithelial ovarian cancer (EOC) has the highest mortality among various types of gynecological malignancies. Most patients die of metastasis and recurrence due to cisplatin resistance. Thus, it is urgent to develop novel therapies to cure this disease. CCK-8 assay showed that nigericin exhibited strong cytotoxicity on A2780 and SKOV3 cell lines. Flow cytometry indicated that nigericin could induce cell cycle arrest at G0/G1 phase and promote cell apoptosis. Boyden chamber assay revealed that nigericin could inhibit migration and invasion in a dose-dependent manner by suppressing epithelial–mesenchymal transition (EMT) in EOC cells. These effects were mediated, at least partly, by the Wnt/β-catenin signaling pathway. Our results demonstrated that nigericin could inhibit EMT during cell invasion and metastasis through the canonical Wnt/β-catenin signaling pathway. Nigericin may prove to be a novel therapeutic strategy that is effective in patients with metastatic EOC.
Keywordsepithelial ovarian cancer nigericin cell cycle epithelial–mesenchymal transition
epithelial ovarian cancer
Unable to display preview. Download preview PDF.
- 12.Goodell, M. A. (2005) Stem cell identification and sorting using the Hoechst 33342 side population (SP), Curr. Protoc. Cytom., Chapt. 9, Unit 9.18.Google Scholar
- 14.Sung, P. L., Jan, Y. H., Lin, S. C., Huang, C. C., Lin, H., Wen, K. C., Chao, K. C., Lai, C. R., Wang, P. H., Chuang, C. M., Wu, H. H., Twu, N. F., Yen, M. S., Hsiao, M., and Huang, C. Y. (2016) Periostin in tumor microenvironment is associated with poor prognosis and platinum resistance in epithelial ovarian carcinoma, Oncotarget, 7, 4036–4047.CrossRefPubMedGoogle Scholar
- 19.Mittag, S., Valenta, T., Weiske, J., Bloch, L., Klingel, S., Gradl, D., Wetzel, F., Chen, Y., Petersen, I., Basler, K., and Huber, O. (2016) A novel role for the tumour suppressor Nitrilase1 modulating the Wnt/beta-catenin signalling pathway, Cell Discov., 2, 15039.CrossRefPubMedPubMedCentralGoogle Scholar