Brief Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Apr 21, 2012; 18(15): 1827-1833
Published online Apr 21, 2012. doi: 10.3748/wjg.v18.i15.1827
KISS-1 inhibits the proliferation and invasion of gastric carcinoma cells
Na Li, Hong-Xing Wang, Jie Zhang, Ya-Ping Ye, Guo-Yang He
Na Li, Jie Zhang, Ya-Ping Ye, Guo-Yang He, Department of Pathology, Xinxiang Medical University, Xinxiang 453003, Henan Province, China
Hong-Xing Wang, Department of Clinical Immunology, Xinxiang Medical University, Xinxiang 453003, Henan Province, China
Author contributions: Li N and Wang HX contributed equally to this work; Li N and Wang HX designed the research experiments; Li N and Zhang J performed the laboratory research, analyzed data and wrote the manuscript; Ye YP and He GY analyzed the data and reviewed the manuscript.
Supported by The Natural Science Foundation, No. 2011A 310005; and the Science and Technique Foundation of Henan Province, No. 112102310206
Correspondence to: Dr. Na Li, Department of Pathology, Xinxiang Medical University, Xinxiang 453003, Henan Province, China. lina@xxmu.edu.cn
Telephone: +86-37-33029123 Fax: +86-37-33029123
Received: April 28, 2012
Revised: August 2, 2011
Accepted: December 8, 2011
Published online: April 21, 2012
Abstract

AIM: 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 mm3) was significantly less than pcDNA3.1 (1250.46 ± 44.36 mm3) and control tumors (1284.36 ± 55.26 mm3) (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).

CONCLUSION: KISS-1 may inhibit the proliferation and invasion of gastric carcinoma cells in vitro and in vivo through the downregulation of MMP-9.

Keywords: KISS-1, Matrix metalloproteinase-9, BGC-823 cells, Proliferation, Metastasis, Nude mice