Abstract: Objective: To explore the effects of OSU-03012 on proliferation and invasion of human colon cancer LoVo cells and the expression of cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2). Methods: The human colon cancer LoVo cells were treated with 0μmol/L, 3μmol/L, 5μmol/L and 10μmol/L of OSU-03012. The proliferation ability of LoVo cells in each group was detected by MTT assay, the invasion ability was detected by Transwell method. The expression of COX-2, VEGF and MMP-2 in LoVo cells were detected by qRT-PCR and Western Blot. Results: The colon cancer LoVo cells were treated with OSU-03012 for 24h, 48h and 72h, the proliferation ability of LoVo cells gradually decreased with the increasing of drug concentration; and pairwise comparison of different concentrations at the same time point showed statistically significant differences (P<0.05). After the LoVo cells were treated with OSU-03012 for 24h of different concentrations, the number of LoVo cells passing through the basilar membrane, as well as COX-2, VEGF, MMP-2 mRNA and protein expression decreased significantly; Pairwise comparison of different concentrations showed statistically significant differences (P<0.05). Conclusions: OSU-03012 can inhibit the proliferation and invasion of human colon cancer LoVo cells, and the molecular mechanisms may be related to down-regulation of COX-2,VEGF and MMP-2 expression.

Key words: OSU-03012, Human colon cancer LoVo cells, Proliferation, Invasion, Cyclooxygenase-2 (COX-2), Vascular endothelial growth factor (VEGF), Matrix metalloproteinase-2 (MMP-2)

摘要： 目的:探讨OSU-03012对人结肠癌LoVo细胞增殖、侵袭及环氧合酶-2(COX-2)、血管内皮生长因子(VEGF)、基质金属蛋白酶-2(MMP-2)表达的影响。方法:分别使用0μmol/L、3μmol/L、5μmol/L、10μmol/L的化合物OSU-03012处理人结肠癌LoVo细胞作为研究对象。MTT法检测各组细胞的增殖能力,Transwell法检测各组细胞的侵袭能力,qRT-PCR法和Western Blot法检测各组细胞COX-2、VEGF、MMP-2的表达情况。结果:OSU-03012作用结肠癌LoVo细胞24h、48h和72h,随着药物浓度的增加LoVo细胞的增殖能力逐渐降低,相同时间点不同浓度间两两比较,差异具有统计学意义（P<0.05）。不同浓度OSU-03012作用LoVo细胞24h,穿过基底膜的LoVo细胞数量,LoVo细胞COX-2、VEGF、MMP-2 mRNA和蛋白的表达明显降低,不同浓度间两两比较差异有统计学意义（P<0.05）。结论:OSU-03012可抑制人结肠癌LoVo细胞的增殖与侵袭,其作用的分子机制可能与下调COX-2、VEGF和MMP-2的表达有关。

关键词: OSU-03012, 人结肠癌LoVo细胞, 增殖, 侵袭, 环氧合酶-2(COX-2), 血管内皮生长因子(VEGF), 基质金属蛋白酶-2(MMP-2)