小分子化合物E-039抑制胃癌细胞迁移侵袭及其分子机制  

The effect and mechanism of E-039 inhibiting the migration and invasion of gastric cancer cells

作　　者：张健[1] 刘彤[1] 李瑞娟[2] 刘奇[1] 李丹妮[3] 李丰[1] 

机构地区：[1]中国医科大学基础医学院细胞生物教研室 教育部医学细胞生物学重点实验室,沈阳110001 [2]沈阳药科大学制药工程学院,沈阳110016 [3]中国医科大学附属第一医院肿瘤内科,沈阳110001

出　　处：《解剖科学进展》2014年第2期105-108,111,共5页Progress of Anatomical Sciences

基　　金：国家自然科学基金资助项目(No.81230077;31371424;81302127)

摘　　要：目的研究小分子化合物E-039对人胃癌细胞增殖、迁移侵袭的影响及其分子机制。方法用MTT检测不同浓度小分子化合物E-039对胃癌细胞BGC823和MKN-45增殖能力的影响。分别用0、20、40、60μmol/L浓度的E-039处理BGC823和MKN-45两种胃癌细胞,应用Transwell小室检测其对上述细胞迁移侵袭能力的抑制作用,Western Blot检测化合物对金属基质蛋白酶2(MMP2)表达及丝切蛋白(Cofilin)磷酸化水平的影响。结果化合物E-039对于BGC823和MKN-45两种胃癌细胞的增殖能力无明显影响,却能够以剂量依赖的方式抑制BGC823及MKN-45细胞的迁移和侵袭。Western Blot结果显示E-039下调胃癌细胞BGC823中MMP2的表达及Cofilin的磷酸化水平。结论化合物E-039能够通过下调胃癌细胞中MMP2的表达及Cofilin的磷酸化水平,抑制胃癌细胞BGC823、MKN-45的迁移和侵袭。Objective To observe the effect and mechanism of E-039 on the proliferation, migration and invasion of human gastric cancer cells. Methods WM＇fT method was used to study the effect of E-039 on the proliferation of BGC823 and MKN-45 cells. The Transwell was used to check the migration and invasion of BGC823 and MKN-45 cells with 0, 20, 40, 60 μmol/L E-039. Western Blotting assay was adopted to identify the effect of E-039 on the expression of matrix metalloproteinase 2（MMP2） and phosphorylated Cofilin. Results E-039 did not affect the proliferation of BGC823 and MKN-45 cells, but could dramatically inhibit the migration and invasion ability of BGC823 and MKN-45 cells in a dose- dependent manner. Furthermore, E-039 could significantly down-regulate the expression levels of MMP2 and phosphorylated Cofilin in BGC823 cells. Conclusion The inhibition of E-039 on the migration and invasion capacity of BGC823 and MKN-45 cells might be related to the down-regulation of the expression levels of MMP2 and phosphorylated Cofilin.

关 键 词：E-039 人胃癌 侵袭 金属基质蛋白酶2 COFILIN 

分 类 号：R735.2[医药卫生—肿瘤]