Hispidulin이 유방암 세포주의 epithelial-mesenchymal transition에 미치는 영향

Abstract

Breast cancer is a leading cause of cancer mortality for women worldwide. However, many anti-cancer drugs have been associated with adverse outcomes. The epithelial to mesenchymal transition (EMT) is the conversion of epithelial cells into mesenchymal cells, which is an important mechanism of epithelial tumor progression, invasion and metastasis. Phytochemicals have been reported to interfere with a specific stage of the carcinogenic process. Herein, we investigated the effect of hispidulin, a polyphenolic flavonoid, on EMT in human breast cancer (MCF-7 and HCC38) cells. Hispidulin inhibited cell proliferation in both MCF-7 and HCC38 cells. Hispidulin (1.25, 2.5 µM) increased the mRNA and protein expression of E-cadherin and occludin and decreased the mRNA and protein expression of vimentin in both breast cancer cells. In addition. co-treatment with hispidulin and TGF-β up-regulated the protein of expression E-cadherin and occludin against TGF-β-induced in MCF-7 and HCC38 cells. The protein expression of vimentin in HCC38 cells were increased after TGF-β treatment, but these effects were reversed by hispidulin and TGF-β co-treatment. We also showed that hispidulin decreased TGF-β-mediated phosphorylation of Smad2/3 in MCF-7 and HCC38 cells. These results revealed that hispidulin inhibits the TGF-β-induced EMT via down-regulation of Smad2/3 signalling pathways of breast cancer cells. Findings from wound-healing and transwell migration experiments provided that hispidulin inhibits TGF-β-mediated migration in MCF-7 and HCC38 cells. These results suggested that the inhibitory effect of migration by hispidulin may be linked with the inhibition of EMT by suppression of Smad2/3 signalling pathways in breast cancer cells.