Thidiazuron decreases epithelial-mesenchymal transition activity through the NF-kB and PI3K/AKT signalling pathways in breast cancer

噻苯隆通过 NF-kB 和 PI3K/AKT 信号通路降低乳腺癌中的上皮-间质转化活性

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作者:Peramaiyan Rajendran, Rebai Ben Ammar, Fatma J Al-Saeedi, Maged Elsayed Mohamed, Mih Islam, Saeed Y Al-Ramadan

Abstract

Breast cancer is the major type among the women population globally. The treatment of cancer metastasis has made modest progress due to multiple factors. Thidiazuron (TDZ) is a novel plant growth regulator that has been shown to have anticancer effects. Therefore, we explored the anti-metastatic potentials of TDZ in cell lines by assessing its potential to suppress the epithelial-mesenchymal transition (EMT). We pretreated the BEAS-2B and breast cancer (MDA-MB-231) cells with TDZ and deliberated alteration in a cell viability, mammosphere, migration, NF-кB signalling, PI3K/AKT signalling and matrix metalloproteinase (MMP) expression and analysed the EMT induction by TGF-β/TNF-α-stimulated BEAS-2B cells. Treatment with TDZ (5-50 μmol) diminished the migration and invasion of the extremely metastatic MDA-MB-231 cells. Additionally, TDZ treatment led to down-regulation of uPAR, uPA, VEGF and MMP-2/-9 expression and up-regulation of TIMP-1/2 expression in these cells. Furthermore, TDZ treatment blocked invasion and EMT in non-tumorigenic BEAS-2B epithelial cells stimulated with TGF-β/TNF-α.TDZ prevents EMT and may thus block metastasis of breast cancer cells.

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