Original Article
Copyright ©2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Oct 28, 2009; 15(40): 5044-5052
Published online Oct 28, 2009. doi: 10.3748/wjg.15.5044
Effects of LY294002 on the invasiveness of human gastric cancer in vivo in nude mice
Chun-Gen Xing, Bao-Song Zhu, Xiao-Qing Fan, Hui-Hui Liu, Xun Hou, Kui Zhao, Zheng-Hong Qin
Chun-Gen Xing, Bao-Song Zhu, Xun Hou, Kui Zhao, Department of General Surgery, The Second Affiliated Hospital, Soochow University, Suzhou 215006, Jiangsu Province, China
Xiao-Qing Fan, Department of General Surgery, The Second Hospital of Jiaxing City, Jiaxing 314000, Jiangsu Province, China
Hui-Hui Liu, Department of Neurology, The Second Affiliated Hospital, Soochow University, Suzhou 215006, Jiangsu Province, China
Zheng-Hong Qin, Laboratory of Aging and Nervous Diseases, Soochow University School of Medicine, Suzhou 215123, Jiangsu Province, China
Author contributions: Xing CG, Zhu BS and Qin ZH designed the research; Xing CG, Zhu BS, Fan XQ, Liu HH, Hou X and Qin ZH wrote the paper; Zhao K collected the analyzed data; Zhu BS selected the color figures in the paper; all authors contributed to the intellectual context and approved the final version.
Supported by The Health Foundation of Jiangsu Province (H200719), the Institution of Higher Education Foundation of Jiangsu Province (08KJB320014) and the Natural Science Foundation of Jiangsu Province (BK2008168)
Correspondence to: Dr. Bao-Song Zhu, Department of General Surgery, The Second Affiliated Hospital, Soochow University, Suzhou 215006, Jiangsu Province, China. baosongzhu@yahoo.com.cn
Telephone: +86-512-67784106 Fax: +86-512-67784106
Received: July 19, 2009
Revised: September 12, 2009
Accepted: September 19, 2009
Published online: October 28, 2009

AIM: To investigate the effects of class I phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 on the invasiveness and related mechanisms of implanted tumors of SGC7901 human gastric carcinoma cells in nude mice.

METHODS: Nude mice were randomly divided into model control groups and LY294002 treatment groups. On days 5, 10 and 15 after treatment, the inhibitory rate of tumor growth, pathological changes in tumor specimens, expression levels of matrix metalloproteinase (MMP)-2, MMP-9, CD34 [representing microvessel density (MVD)] and vascular endothelial growth factor (VEGF), as well as apoptosis indexes in tumor samples were observed.

RESULTS: In this study, we showed that treating the tumors with LY294002 could significantly inhibit carcinoma growth by 11.3%, 29.4% and 36.7%, after 5, 10 and 15 d, respectively, compared to the control group. Hematoxylin & eosin staining indicated that the rate of inhibition increased progressively (23.51% ± 3.11%, 43.20% ± 3.27% and 63.28% ± 2.10% at 5, 10 and 15 d, respectively) along with apoptosis. The expression of MMP-2 was also downregulated (from 71.4% ± 1.6% to 47.9% ± 0.7%, 31.9% ± 0.9% and 7.9% ± 0.7%). The same effects were observed in MMP-9 protein expression (from 49.4% ± 1.5% to 36.9% ± 0.4%, 23.5% ± 0.9% and 7.7% ± 0.6%), the mean MVD (from 51.2% ± 3.1% to 41.9% ± 1.5%, 30.9% ± 1.7% and 14.9% ± 0.8%), and the expression of VEGF (from 47.2% ± 3.1% to 25.9% ± 0.5%, 18.6% ± 1.2% and 5.1% ± 0.9%) by immunohistochemical staining.

CONCLUSION: The class I PI3K inhibitor LY294002 could inhibit the invasiveness of gastric cancer cells by downregulating the expression of MMP-2, MMP-9, and VEGF, and reducing MVD.

Keywords: Phosphatidylinositol 3-kinase, LY294002, Gastric cancer, Neoplasm invasiveness