title: KISS-1 inhibits the proliferation and invasion of gastric carcinoma cells.
abstract: OBJECTIVE
  To investigate the function of the KISS-1 gene in gastric carcinoma cells and to explore its potential mechanism.
  
  
  METHODS
  A KISS-1 eukaryotic expression vector was constructed and transfected into BGC-823 cells. Resistant clones were obtained through G418 selection. reverse transcription-polymerase chain reaction and western blotting were used to detect KISS-1 and matrix metalloproteinase-9 (MMP-9) expression in transfected cells. The growth of transfected cells was investigated by 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) proliferation assays, and the cells' invasive potential was analyzed by basement membrane (Matrigel) invasion assays. The anti-tumor effects of KISS-1 were tested in vivo using allografts in nude mice.
  
  
  RESULTS
  The expression level of KISS-1 mRNA and protein in BGC-823/KISS-1 transfected cells were significantly higher than in BGC-823/pcDNA3.1 transfected cells (P < 0.05) or the parental BGC-823 cell line (P < 0.05). The expression level of MMP-9 mRNA and protein in BGC-823/KISS-1 were significantly less than in BGC-823/pcDNA3.1 (P < 0.05) or BGC-823 cells (P < 0.05). MTT growth assays show the proliferation of BGC-823/KISS-1 cells at 48 h (0.642 ± 0.130) and 72 h (0.530 ± 0.164) were significantly reduced compared to BGC-823/pcDNA3.1 (0.750 ± 0.163, 0.645 ± 0.140) (P < 0.05) and BGC-823 cells (0.782 ± 0.137, 0.685 ± 0.111) (P < 0.05). Invasion assays indicate the invasive potential of BGC-823/KISS-1 cells (16.50 ± 14.88) is significantly reduced compared to BGC-823/pcDNA3.1 (20.22 ± 14.87) (P < 0.05) and BGC-823 cells after 24 h (22.12 ± 16.12) (P < 0.05). In vivo studies demonstrate the rate of pcDNA3.1-KISS-1 tumor growth is significantly slower than pcDNA3.1 and control cell tumor growth in nude mice. Furthermore, tumor volume of pcDNA3.1-KISS-1 tumors (939.38 ± 82.08 mm(3)) was significantly less than pcDNA3.1 (1250.46 ± 44.36 mm(3)) and control tumors (1284.36 ± 55.26 mm(3)) (P < 0.05). Moreover, the tumor mass of pcDNA3.1-KISS-1 tumors (0.494 ± 0.84 g) was significantly less than pcDNA3.1 (0.668 ± 0.55 g) and control tumors (0.682 ± 0.38 g) (P < 0.05).
  
  
  CONCLUSIONS
  KISS-1 may inhibit the proliferation and invasion of gastric carcinoma cells in vitro and in vivo through the downregulation of MMP-9.
authors.affiliation: Department of Pathology, Xinxiang Medical University, Xinxiang 453003, Henan Province, China. lina@xxmu.edu.cn
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Hong-Xing
authors.initials: HX
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Ye
authors.forename: Guo-Yang
authors.initials: GY
authors.lastname: He
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D059648:Kisspeptins / Q000235:genetics / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D010957:Plasmids; D013274:Stomach Neoplasms / Q000473:pathology*; D014162:Transfection
chemical_list: C106628:KISS1 protein, human; D059648:Kisspeptins; D061965:Matrix Metalloproteinase Inhibitors; D020780:Matrix Metalloproteinase 9