Effects of LY294002 on the invasiveness of human gastric cancer in vivo in nude mice.
OBJECTIVE
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.


CONCLUSIONS
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.
Department of General Surgery, The Second Affiliated Hospital, Soochow University, Suzhou 215006, Jiangsu Province, China.
Chun-Gen
CG
Xing
Bao-Song
BS
Zhu
Xiao-Qing
XQ
Fan
Hui-Hui
HH
Liu
Xun
X
Hou
Kui
K
Zhao
Zheng-Hong
ZH
Qin
D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis; D017209:Apoptosis; D002867:Chromones / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D051379:Mice; D008819:Mice, Nude; D009025:Morpholines / Q000494:pharmacology*; D009368:Neoplasm Transplantation; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D018952:Antigens, CD34; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9