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

Abstract

Background: Vascular endothelial growth factor and matrix metalloproteinases are two important factors for angiogenesis associated with breast cancer growth and progression. The present study was aimed to examine the effects of tamoxifen and tranilast drugs singly or in combination on proliferation of breast cancer cells and also to evaluate VEGF and MMP-9 expression and VEGF secretion levels. Materials and Methods: Human breast cancer cell lines, MCF-7 and MDA-MB-231, were treated with tamoxifen and/or tranilast alone or in combination and percentage cell survival and proliferative activity were evaluated using LDH leakage and MTT assays. 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 a significant 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 rarely increased MMP-9 expression. A decrease in MMP-9 expression was seen after treatment with tranilast alone and in the combined treatment MMP-9 mRNA level was decreased. Conclusions: This combination treatment can able to inhibit growth, proliferation and angiogenesis of breast cancer cells.

Cinobufacin Suppresses Cell Proliferation via miR-494 in BGC-823 Gastric Cancer Cells

“…Many studies have demonstrated that MMP-9 (Hassan et al, 2012;Zhang et al, 2012;Akdeniz et al, 2013;Asuthkar et al, 2013;Darakhshan et al, 2013;Li et al, 2013), ERK1/2 (Romano et al, 2012), KIT (Kim et al, 2011) and PTEN are considered to be the potential targeted genes of miR-494. In present study, BAG-1 is predicted as the targeted gene of miR-494 by using bioinformatics tools TargetScan, PicTar, and Miranda.…”

Radixin Knockdown by RNA Interference Suppresses Human Glioblastoma Cell Growth in Vitro and in Vivo

“…MMPs are overexpressed not only by glioma cell lines but also by the tumor vasculature, suggesting a relevant role in angiogenesis induction and regulation (Liotta et al, 1991;Hanahan and Folkman, 1996). MMP9 are overexpressed also in many other tumors, such as in osteosarcomas (Jin et al, 2013), breast cancer (Darakhshan et al, 2013), cholangiocarcinoma (Kidoikhammouan et al, 2013), human fibrosarcoma cell (Yahayo et al, 2013), which all are overexpressed, suggesting a relevant role in tumor angiogenesis, growth, and invasion. Our results showed that MMP9 expressions were markedly decreased in Lenti-radixin cells in vitro.…”

Tranilast: A review of its therapeutic applications

“…It was found to significantly reduce VEGF/VPF-induced vascular permeability [130]. Tranilast had an anti-angiogenic effect on lung carcinoma cells [91], and suppressed VEGF expression and secretion in breast cancer cells [131]. Furthermore, it had anti-angiogenic or anti-VEGF-induced chemotactic effects in autoimmune disease models [7].…”