Interplay of Interleukin-1β and Curcumin on VEGF Expression in Breast Cancer Cells

Background: VEGF regulates tumor vascularization in response to hypoxia and inflam-matory signals while curcumin is anti-inflammatory. We investigated this interaction in breast cancer cell lines and gene expression databases. Methods: VEGF in cell cultures was detected by ELISA. Kinase activation was investigated by Western blotting. Gene ex-pression databases were analyzed by correlation tests. Results: VEGF secretion and kinase signaling in response to IL-1β and curcumin varied significantly for the cell lines. All cell lines increased VEGF secretion under hypoxia, but IL-1β increased VEGF secretion only in MCF-7 cells. VEGF secretion was inhibited by curcumin in MDA-MB-231 cells but in-creased in MCF-7- and UACC-3199 cells. Inhibitor experiments in MCF-7 cells demon-strated that curcumin-induced ERK- phosphorylation was important for VEGF secretion. In a retrospective cohort, VEGF detected by immunohistochemistry correlated with ductal- versus lobular morphology but showed no prognostic significance. Gene expression data of the METABRIC study showed highest VEGFA mRNA expression in triple negative breast cancer. Analysis of HIF-, NF-kB-signaling and VEGF expression on the mRNA level showed no clear correlation but suggested crosstalk of these pathways. Conclusion: These dissimilar responses of breast cancer cell lines suggest that therapy efficiency with an-ti-VEGF, anti-IL-1β or curcumin will also vary within breast cancers.