Abstract P2-09-19: Zerumbone suppresses IL-1b-induced cell migration and invasion through inhibition of IL-8 expression and MMP3 expression in human triple negative breast cancer cells

Abstract

Abstract Background: Inflammation is a key regulatory process in breast cancer progression and severity. Several studies have demonstrated that prolonged exposure of breast tumor cells to inflammatory cytokines leads to epithelial-mesenchymal transitions (EMT), which is the principle mechanism involved in metastasis and tumor invasion. Disruption of the signaling pathways involved in EMT may therefore provide an effective treatment strategy for currently difficult to treat or untreatable cancers such as TNBC. The interleukin (IL)-1 plays a pivotal role on breast cancer proliferation, invasion and/or inflammation. Here, we investigated the correlation of MMP-3 and IL-8 on IL-1b-induced cell migration and invasion as well as the inhibitory effect of zerumbone on IL-1β-induced MMP-3 and IL-8. Methods: Triple negative breast cancer cells (Hs578T and MDA-MB231) were cultured DMEM with 10% FBS and 1% antibiotics. The levels of IL-8 and MMP-3 mRNA were analyzed by real-time PCR. The levels of secreted IL-8 and MMP-3 protein expression were analyzed by ELISA and western blot analysis, respectively. Cell viabilities by drug were analyzed by MTT assay. Cell invasion and migration was detected by Boyden chamber assay. Results: The level of IL-8 and MMP-3 mRNA and protein expression significantly increased by IL-1β treatment in both Hs578T cells and MDA-MB231 cells. In addition, IL-1β-induced cell migration and invasion also increased in Hs578T and MDA-MB231 cells. On the other hand, the levels of basal and IL-1β-induced IL-8 and MMP-3 expression were decreased by zerumbone. Conclusion: IL-1β induces the migration and invasion of breast cancer cells through IL-8 and MMP-3 expression. These effects are significantly suppressed by zerumbone. Therefore, we suggest that zerumbone may act as a useful therapeutic agent for treatment of triple negative breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-09-19.