肝细胞生长因子和MAPK途径在大肠癌细胞体外侵袭中的作用

Effect of hepatocyte growth factor/scatter factor and MAPK pathway on the invasion of colorectal cancer cells in vitro

目的:探讨肝细胞生长因子/离散因子(HGF/SF)在大肠癌细胞体外侵袭中的作用。方法:用细胞迁移系统分析HGF、PD98059和SB203580处理的大肠癌细胞Caco-2和Colo320体外迁移能力;用逆转录聚合酶链反应检测Caco-2细胞中MMP-2、MMP-9及其抑制因子TIMP-1、TIMP-2的mRNA表达。结果:HGF对Colo320细胞迁移无影响。细胞培养48 h后,Caco-2细胞迁移数HGF组和PD98059组与对照组比较、HGF组和PD98059组比较,差异显著[对照组(104.40±4.77/)ml,HGF/SF组(126.80±5.40/)ml,PD98059组(82.80±4.15/)ml,P<0.01]。HGF组MMP-2、MMP-9、TIMP-1、TIMP-2都有表达,MMP-2高表达;PD98059组TIMP-1和TIMP-2高表达。结论:HGF促使Caco-2细胞迁移。HGF/SF上调Caco-2细胞中MMP-2和MMP-9的表达,使肿瘤细胞破坏周围基底膜能力增强而容易形成转移。HGF对某些大肠癌细胞发挥促进侵袭、促进转移的作用,MAPK途径在HGF/SF诱导的大肠癌细胞Caco-2中发挥生物学效应。

Objective： To investigate the role of hepatocyte growth factor/scatter factor （HGF/SF） in the invasion of colorectal cancer cells in vitro. Methods： Mathods：Matrigel migration assay was used to analyze the migration ability in vitro of the colorectal cancer cell lines Caco-2 and Colo320, which were treated with HGF, PD98059 （the inhibitor of p42/p44MAPK）, and SB203580 （the inhibitor of p38MAPK）, respectively. The mRNA expression levels of MMP-2 and MMP-9 and their natural inhibitors TIMP-1 and TIMP-2 in Caco-2 cells were determined by reverse transcription polymerase chain reaction. Results： HGF did not affect the migration ability of Colo320 cells. After 48-hour incuba- tion, significant differences in the number of Caco-2 cells migrated were found between HGF group and control group, PD98059 group and control group, and HSF gxoup and PD98059 group （control group 104.40±4.77/ml, HGF/SF group 126.80±5.40/ml, PD98059 group 82.80±4.15/ml, all P〈 0.01）. In HGF group, the expressions of MMP-2, MMP-9, TIMP-1, and TIMP-2 mRNA were found, and MMP-2 mRNA was highly expressed. TIMP-1 and TIMP-2 mRNA were highly expressed in PD98059 group. Conclusion： HGF could promote Caco-2 migration. HGF/SF up-regulates the expressions of MMP-2 and MMP-9 in Caco-2 cells and promotes the migration of cancer cells into extracellular matrix and the development of metastasia.p42/p44 MAPK pathway has biological effects on Caco-2 cells induced by HGF/SF.