FoxM1 as a potential therapeutic target for triple-negative breast cancer.

Abstract

e22063 Background: Elevated expression or activity of the transcription factor forkhead box M1 (FoxM1) is associated with development and progression of breast cancer. In this study, we show that whether inhibition of FoxM1 in triple negative breast cancer (TNBC) cell lines causes the changes of cancer progress and response to the treatment. Methods: We inhibited FoxM1 using thiostrepton (FoxM1 inhibitor) and identified the activity of VEGF, cyclin B, cyclin D1, p27, CD44 and cleaved capase-3 in MDA-MB-231 cells. Invasion assay was evaluated in BT-20 cells and combination with cisplatin and inhibition of FoxM1 were treated in triple negative breast cancer (TNBC) cell lines including MDA-MB-231, MDA-MB-157, and BT-20. Results: When FoxM1 was inhibited using thiostrepton in MDA-MB-231 cells, expressions of VEFG, cyclin B, cyclin D1, p27, and CD44 were decreased. On the other hand, cleaved caspase-3 expression was increased. Intersetingly, response to inhibition of FoxM1 depended on the expression of p53 in each cell lines. Invasiveness of BT-20 cells is markedly reduced by inhibitioh of FoxM1. Co-treatment with thiotrepton and cisplatin synergistically induced apoptosis of breast cancer cells in MDA-MB-231, MDA-MB-157, and BT-20. Conclusions: Inhibition of FoxM1 increases apoptosis and decreases invasiveness and VEGF exprsssion of TNBC cells. And when inhibition of FoxM1 combines with cisplatin treament, synergistic effect was shown. Therefore, FoxM1 is valuable as a potential target for not only anticancer activity but also overcoming cisplatin resistance in TNBC.