BioScience Trends. 2018;12(1):40-46. (DOI: 10.5582/bst.2017.01288)
FL118, a novel camptothecin analogue, suppressed migration and invasion of human breast cancer cells by inhibiting epithelialmesenchymal transition via the Wnt/β-catenin signaling pathway.
Yang ZH, Ji LX, Jiang GH, Liu RR, Liu ZT, Yang YC, Ma QX, Zhao HQ
The aim of the current study was to investigate the effects of FL118, a novel camptothecin analogue, on migration and invasion of human breast cancer cells and the underlying mechanisms of those effects. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and a plate clone formation assay were used to examine inhibition of the proliferation of MDA-MB-231 cells by FL118. Cell cycle distribution was detected using flow cytometry. A wound healing assay and a transwell assay were performed to detect the effects of FL118 on migration and invasion of MDA-MB-231 cells, respectively. qRTPCR, Western blotting, and immunocytochemistry were used to study the effects of FL118 on expression of epithelial-mesenchymal transition (EMT)-related molecules and Wnt/β-catenin signaling components in MDA-MB-231 cells. The current results indicated that FL118 inhibited the proliferation, migration and invasion of MDA-MB-231 cells in a dose and time-dependent manner. FL118 caused MDA-MB-231 cells to accumulate in the S phase. FL118 significantly suppressed the expression of vimentin while enhancing the expression of E-cadherin. Moreover, decreased expression of β-catenin and its targets survivin and cyclin Dl was detected in the nucleus of MDA-MB-231 cells. Taken together, the current results suggest that FL118 inhibited Wnt/β-catenin signaling, leading to suppressed EMT and decreased migration and invasion of breast cancer cells.