Targeting the IGF1/Twist1 axis: A novel mechanism for β-elemene-induced anoikis and EMT inhibition in breast cancer cells.

[BACKGROUND] Anoikis resistance and epithelial-mesenchymal transformation (EMT) promote breast cancer spread. There is a positive correlation between twist family BHLH transcription factor 1 (Twist1) and anoikis resistance. Given the demonstrated therapeutic effect of β-elemene treatment on breast cancer, its effects on Twist1 and anoikis became the focus of our research.

[METHODS] Breast cancer cells, MDA-MB-157 and MDA-MB-231, were treated with 25 and 50 μM concentrations of β-elemene. Breast cancer cell lines with insulin-like growth factor 1 (IGF1) overexpression and Twist1 knockdown were successfully constructed to further explore the relevant mechanisms. Cell viability and apoptosis were detected by cell counting kit 8 (CCK8) method and fluorescent staining, respectively. Scratch assay for the detection of cell migration ability. The expression levels of matrix metalloproteinase (MMP) 9, MMP2, vimentin, N-cadherin, E-cadherin, Twist1, IGF1 and other related proteins were measured by western blot.

[RESULTS] β-elemene reduced cell viability and produced anoikis in a concentration-dependent manner. β-elemene decreased the expressions of MMP9 and MMP2, inhibited vimentin, N-cadherin, Twist1, IGF1 expressions and cell migration ability, and up-regulated E-cadherin. The overexpression of IGF1 reversed the regulatory effects of β-elemene on cell survival, anoikis, cell migration and associated protein expressions, but the knockdown of Twist1 can counteract the impact of IGF1 overexpression.

[CONCLUSION] β-elemene modulates anoikis and EMT in breast cancer cells via the IGF1/Twist1 signaling pathway, offering novel insights for breast cancer therapy.