Synergistic Effects of Tamoxifen and Tranilast on VEGF and MMP-9 Regulation in Cultured Human Breast Cancer Cells

Background: Vascular endothelial growth factor and matrix metalloproteinases are two important factorsfor angiogenesis associated with breast cancer growth and progression. The present study was aimed to examinethe effects of tamoxifen and tranilast drugs singly or in combination on proliferation of breast cancer cells andalso to evaluate VEGF and MMP-9 expression and VEGF secretion levels. Materials and
Methods: Humanbreast cancer cell lines, MCF-7 and MDA-MB-231, were treated with tamoxifen and/or tranilast alone or incombination and percentage cell survival and proliferative activity were evaluated using LDH leakage and MTTassays. mRNA expression and protein levels were examined by real-time RT-PCR and ELISA assay, respectively.
Results: LDH and MTT assays showed that the combined treatment of tamoxifen and tranilast resulted in asignificant decrease in cell viability and cell proliferation compared with tamoxifen or tranilast treatment alone,with significant decrease in VEGF mRNA and protein levels. We also found that tamoxifen as a single agent rarelyincreased MMP-9 expression. A decrease in MMP-9 expression was seen after treatment with tranilast aloneand in the combined treatment MMP-9 mRNA level was decreased.
Conclusions: This combination treatmentcan able to inhibit growth, proliferation and angiogenesis of breast cancer cells.