水飞蓟素通过MAPK通路调控非小细胞肺癌细胞MMP2、MMP9表达及侵袭的研究  

Silymarin regulates the expression of MMP2,MMP9 and invasion of non-small cell lung cancer cells through MAPK pathway

作　　者：唐寅[1] 耿智馨 宋爱英[1] 韩笑[1] Tang Yin;Geng Zhixin;Song Aiying;Han Xiao(Department of Oncology,the First Affiliated Hospital,Heilongjiang University of Chinese Medicine,Harbin 150040,China;Department of Rehabilitation,the Second Affiliated Hospital,Heilongjiang University of Chinese Medicine,Harbin 150040,China)

机构地区：[1]黑龙江中医药大学附属第一医院肿瘤科,哈尔滨1500402 [2]黑龙江中医药大学附属第二医院康复科,哈尔滨150040

出　　处：《国际呼吸杂志》2022年第17期1343-1349,共7页International Journal of Respiration

基　　金：黑龙江省中医药科研项目(ZHY2020-105)。

摘　　要：目的研究水飞蓟素(SM)通过丝裂原活化蛋白激酶(MAPK)通路调控非小细胞肺癌(NSCLC)细胞基质金属蛋白酶(MMP)、MMP9表达及侵袭的作用。方法本研究为实验研究,培养NSCLC细胞并分组给药,以不含药物培养基处理的细胞作为对照组,给予不同剂量SM(10、20、40 mg/L)、40 mg/L SM联合10μmol/L p38 MAPK拮抗剂SB203580或10μmol/L JNK拮抗剂SP600125处理。24 h后检测侵袭数目,MMP2及MMP9的mRNA表达水平及活性,ERK1/2、p38、JNK的激活程度。结果与对照组比较,10、20、40 mg/L能够以剂量依赖性的方式降低细胞侵袭数目[(324.59±52.31)比(242.33±34.32)、(175.56±25.42)、(121.23±21.23),F=18.33,P<0.01]、MMP2[(1.00±0.00)比(0.67±0.09)、(0.40±0.06)、(0.19±0.03),F=23.82、P<0.01]及MMP9[(1.00±0.00)比(0.74±0.13)、(0.54±0.07)、(0.34±0.06),F=20.71、P<0.01]的mRNA表达水平及活性,增加p-p38[(1.00±0.00)比(0.88±0.10)、(0.74±0.07)、(0.40±0.06),F=13.82、P<0.01]、p-JNK[(1.00±0.00)比(0.71±0.13)、(0.50±0.07)、(0.30±0.05),F=19.941、P<0.01]的表达水平,但不影响p-ERK1/2的表达(P>0.05);与溶剂+40 mg/L SM组比较,40 mg/L SM干预的同时加用拮抗剂SB203580或SP600125能够增加细胞侵袭数目及MMP2、MMP9的mRNA表达水平及活性。结论SM对NSCLC细胞MMP2、MMP9的表达及侵袭具有抑制作用,这一抑制作用与激活p38MAPK、JNK通路有关。Objective To study the effect of silymarin(SM)on the expression of matrix metalloproteinase(MMP)2,MMP9 and invasion of non-small cell lung cancer(NSCLC)cells through mitogen activated protein kinase(MAPK)pathway.Methods This study was an experimental study.NSCLC cells were cultured and treated in groups.Cells treated in drug-free media as a control group,and given different doses of SM(10 mg/L,20 mg/L,40 mg/L),40 mg/L SM combined with 10μmol/L p38MAPK antagonist SB203580 or 10μmol/L JNK antagonist SP600125.After 24 hours,the number of invasion,the mRNA expression and activity of MMP2 and MMP9,and the activation degree of ERK1/2,p38 and JNK were detected.Results Compared with the control group,10 mg/L,20 mg/L and 40 mg/L SM could decrease the number of cell invasion[(324.59±52.31)vs(242.33±34.32),(175.56±25.42),(121.23±21.23),F=18.33,P<0.01],the mRNA expression and activity of MMP2[(1.00±0.00)vs(0.67±0.09),(0.40±0.06),(0.19±0.03),F=23.822,P<0.01]and MMP9[(1.00±0.00)vs(0.74±0.13),(0.54±0.07),(0.34±0.06),F=20.714,P<0.01],and increase the expression levels of p-p38[(1.00±0.00)vs(0.88±0.10),(0.74±0.07),(0.40±0.06),F=13.822,P<0.01]and p-JNK[(1.00±0.00)vs(0.71±0.13),(0.50±0.07),(0.30±0.05),F=19.941,P<0.01]on a dose-dependent manner,but did not affect the expression of p-ERK1/2(P>0.05).Compared with the solvent+40 mg/L SM group,40 mg/L SM combined with SB203580 or SP600125 could increase the number of cell invasion and the mRNA expression and activity of MMP2 and MMP9.Conclusions SM can inhibit the expression of MMP2 and MMP9 and invasion of NSCLC cells,which is related to the activation of p38MAPK and JNK pathway.

关 键 词：癌 非小细胞肺 水飞蓟素 基质金属蛋白酶 侵袭 丝裂原活化蛋白激酶 

分 类 号：R734.2[医药卫生—肿瘤]