title: 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.
  
  
  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.
authors.affiliation: Department of Biology, Faculty of Science, Razi University, Kermanshah, Iran E-mail : aghanbari@kums.ac.ir.
authors.forename: Sara
authors.initials: S
authors.lastname: Darakhshan
authors.forename: Ali
authors.initials: A
authors.lastname: Bidmeshkipour
authors.forename: Mozafar
authors.initials: M
authors.lastname: Khazaei
authors.forename: Arezou
authors.initials: A
authors.lastname: Rabzia
authors.forename: Ali
authors.initials: A
authors.lastname: Ghanbari
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018931:Antineoplastic Agents, Hormonal; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D062367:ortho-Aminobenzoates; D013629:Tamoxifen; D007770:L-Lactate Dehydrogenase; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C012293:tranilast