7-ethyl-7-hydroxy-10h-1-3-dioxolo(4-5-g)pyrano(3--4--6-7)indolizino(1-2-b)quinoline-8-11(7h-12h)-dione and Breast-Neoplasms

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. qRT-PCR, 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.

Topics: Benzodioxoles; beta Catenin; Breast Neoplasms; Cadherins; Camptothecin; Cell Cycle; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cyclin D; Epithelial-Mesenchymal Transition; Female; Humans; Indolizines; Inhibitor of Apoptosis Proteins; Neoplasm Invasiveness; Survivin; Vimentin; Wnt Signaling Pathway