Objective  To investigate the mechanism by which the microtubule inhibitor VERU-111 inhibits epithelial-mesenchymal transition (EMT) through regulation of the transforming growth factor-β (TGF-β) pathway, thereby reducing the proliferation and metastasis of ovarian cancer cells.

Methods  Ovarian cancer cell lines OVCAR3 and SKOV3 were used as research subjects. The cells were divided into four groups: the control group, the low-dose VERU-111 group, the high-dose VERU-111 group, and TGF-β activator group. Cell proliferation was assessed using the MTT assay, colony formation assay was used to evaluate clonogenic ability, and migration assay was used to analyze cell migratory characteristics. Western blotting was used to detect proteins related to the TGF-β signaling pathway and EMT markers.

Results  Compared with the control group, VERU-111 treatment significantly reduced the proliferation, colony formation, and migration abilities of OVCAR3 and SKOV3 ovarian cancer cells (P<0.05). Additionally, VERU-111 markedly inhibited the phosphorylation levels of key proteins in the TGF-β and its downstream signaling pathways, such as Smad2/3, and decreased the expression of mesenchymal markers, such as N-cadherin and vimentin. It also increased the expression of the epithelial marker E-cadherin (P<0.05).

Conclusion  The microtubule inhibitor VERU-111 significantly suppresses the proliferation and migration of ovarian cancer cells OVCAR3 and SKOV3 by regulating the TGF-β pathway to inhibit the EMT process, suggesting its potential therapeutic application value.

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