Inhibitory effects of resistin-13-peptide on the proliferation, adhesion, and invasion of MDA-MB-231 in human breast carcinoma cells

Endocr Relat Cancer. 2007 Dec;14(4):1063-71. doi: 10.1677/erc.1.01304.

Abstract

To investigate the potential effects of resistin-13-peptide on the growth, adhesion, and invasion in human breast carcinoma cells, MDA-MB-231. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay and colony-forming assay were used to assess the proliferation effects of resistin-13-peptide. The adhesive ability was investigated by cell adhesion assay, and the invasive potential was assessed using a transwell model. Activities of matrix metalloproteinase (MMP)-2 and MMP-9 were measured by zymography analysis and western blotting. Tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 were determined by western blotting. In this study, we performed in vivo experiments and determined the effect of resistin-13-peptide on tumor growth and other organs, especially ovaries in a xenograft model using the cell line studied. Resistin-13-peptide inhibited MDA-MB-231 cell growth and colony formation in a dose- and time-dependent manner. Meanwhile, the invasive and adhesive abilities of MDA-MB-231 cells were yet cut down by resistin-13-peptide in a dose-dependent manner. Resistin-13-peptide decreased the gelatinolytic activities of both MMP-2 and MMP-9 and enhanced the protein expression of TIMP-1 and TIMP-2, which were secreted from the MDA-MB-231 cells. The animal experiments found that the growth of tumors was repressed by resistin-13-peptide, which affected other organs in the same time. Especially, ovaries did not have pathological changes yet. Treatment with resistin-13-peptide is effective in suppressing tumor proliferation, adhesion, and invasion. The possible mechanism is downregulation of MMPs and upregulation of TIMPs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / pathology*
  • Cell Adhesion / drug effects*
  • Cell Division / drug effects*
  • Cell Line, Tumor
  • Colony-Forming Units Assay
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness*
  • Peptide Fragments / pharmacology*
  • Resistin / pharmacology*
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism

Substances

  • Peptide Fragments
  • Resistin
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-2
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9