Inhibitory effects of resistin-13-peptide on the proliferation, adhesion, and invasion of MDA-MB-231 in human breast carcinoma cells.
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.
Institute of Radiation Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Tianjin 300192, China.
Bing
B
Pan
Ming-Hui
MH
Zhao
Zhong
Z
Chen
Lu
L
Lu
Yan
Y
Wang
Da-Wei
DW
Shi
Pei-Zhen
PZ
Han
D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D010446:Peptide Fragments / Q000494:pharmacology*; D052243:Resistin / Q000494:pharmacology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
D010446:Peptide Fragments; D052243:Resistin; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9