Department of General Surgery, The Second Affiliated Hospital, Soochow University, Suzhou 215006, Jiangsu Province, China.
World J Gastroenterol. 2009 Oct 28;15(40):5044-52. doi: 10.3748/wjg.15.5044.
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.
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.
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.
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.
研究 I 类磷酸肌醇 3-激酶（PI3K）抑制剂 LY294002 对人胃癌 SGC7901 细胞裸鼠种植瘤侵袭性及相关机制的影响。
裸鼠随机分为模型对照组和 LY294002 治疗组，治疗后第 5、10、15 天，观察抑瘤率、肿瘤组织病理变化、基质金属蛋白酶（MMP）-2、MMP-9、CD34[代表微血管密度（MVD）]、血管内皮生长因子（VEGF）的表达水平以及肿瘤组织的凋亡指数。
本研究表明，与对照组相比，LY294002 治疗后第 5、10、15 天肿瘤生长抑制率分别为 11.3%、29.4%和 36.7%。苏木精-伊红（HE）染色表明抑制率逐渐升高（第 5、10、15 天分别为 23.51%±3.11%、43.20%±3.27%和 63.28%±2.10%），同时伴随着细胞凋亡。MMP-2 的表达也下调（从 71.4%±1.6%降至 47.9%±0.7%）。MMP-9 蛋白表达也观察到相同的效果（从 49.4%±1.5%降至 36.9%±0.4%），平均 MVD（从 51.2%±3.1%降至 41.9%±1.5%）和 VEGF 表达（从 47.2%±3.1%降至 25.9%±0.5%）。
I 类 PI3K 抑制剂 LY294002 可能通过下调 MMP-2、MMP-9 和 VEGF 的表达，降低 MVD，抑制胃癌细胞的侵袭性。
