摘要
目的探讨褪黑素(MLT)对胃癌细胞迁移和侵袭的抑制作用及其分子机制。方法不同浓度(0.1、1、2和4 mmol/L)的褪黑素干预人胃癌SGC-7901细胞24 h,应用划痕实验、Transwell小室法检测胃癌细胞迁移和侵袭能力的改变;ELISA试剂盒检测培养液上清中基质金属蛋白酶(MMP)-2、MMP-9的表达,Real-time PCR检测胃癌细胞MMP-2、MMP-9、细胞间黏附分子1(ICAM-1)和CD44基因表达;免疫印迹法检测ICAM-1、CD44、p-P38、P38和磷酸化丝裂原活化蛋白激酶激酶(p-MKK)3/6蛋白表达。结果褪黑素抑制胃癌细胞的迁移和侵袭,并呈剂量依赖性。与空白对照组比较,褪黑素降低胃癌细胞基质金属蛋白酶(MMP)-2、MMP-9和ICAM-1、CD44的表达,并抑制p-P38、P38和p-MKK3/6的表达。结论褪黑素通过抑制胃癌细胞MMP-2、MMP-9、ICAM-1和CD44的表达从而抑制胃癌细胞的迁移和侵袭能力,抑制作用可能与p38MAPK信号通路有关。
Objective To investigate the inhibitory effect of melatonin on the migration and invasion of gastric cancer cell and the underlying molecular mechanism.Methods Human gastric cancer SGC-7901 cells were treated with different concentrations of melatonin(0.1,1,2 and 4 mmol/L)for 24 hours,and the changes in the migration and invasion of gastric cancer cells were detected by scratch test and Transwell assay.The expressions of matrix metalloproteinase(MMP)-2 and MMP-9 in the supernatant were detected by ELISA kit.The changes of MMP-2,MMP-9,intercellular cell adhesion molecule-1(ICAM-1)and CD44 expressions were detected by using Real-time PCR.The protein expressions of ICAM-1,CD44,p-P38,P38 and phosphorylated mitogen-activated protein kinase kinase(p-MKK)3/6 were detected by Western blotting.Results Melatonin inhibited the migration and invasion of gastric cancer cells in a dosedependent manner.Compared with the blank control group,melatonin reduced the expression of MMP-2,MMP-9,ICAM-1 and CD44,and inhibited the expressions of p-P38,P38 and p-MKK3/6 in gastric cancer cells.Conclusion Melatonin inhibits the migration and invasion of gastric cancer cells by inhibiting the expressions of MMP-2,MMP-9,ICAM-1 and CD44.Inhibition may be related to the p38 MAPK signaling pathway.
作者
徐丽
金清东
陈秀娇
陈超
郑伟男
周瑞祥
XU Li;JIN Qing-dong;CHEN Xiu-jiao;CHEN Chao;ZHENG Wei-nan;ZHOU Rui-xiang(Basic Medical College of Putian University,Fujian Putian 351100,China;Department of Neurosurgery,Putian First Hospital,Fujian Putian 351100,China;Department of Human Anatomy and Histology and Embryology,Neurobiology Research Center,Fujian Medical University,Fuzhou 350004,China)
出处
《解剖学报》
CAS
CSCD
北大核心
2021年第5期751-758,共8页
Acta Anatomica Sinica
基金
福建省自然科学基金(2016J01403)
国家卫生计生委共建科学研究基金-福建省卫生教育联合攻关计划项目(WKJ-FJ-37)
莆田学院育苗课题(2014059)。
