PKC介导P38MAPK通路调控结直肠癌细胞MMP-9表达及侵袭的研究  

Study of PKC mediated P38MAPK pathway on regulating MMP-9 expression and invasion in colorectal cancer cells

作　　者：姜媛[1] 谢海娟 王毓兴 白鹰[2] 俞红女[2] JIANG Yuan;XIE Haijuan;WANG Yuxing;BAI Ying;YU Hongnv(Department of Medical Oncology,Dalian University Affiliated Xinhua Hospital,Dalian116000,China;Central Laboratory,Dalian University Affiliated Xinhua Hospital,Dalian116000,China)

机构地区：[1]大连大学附属新华医院肿瘤内科,辽宁大连116000 [2]大连大学附属新华医院中心实验室,辽宁大连116000

出　　处：《中国现代医生》2020年第26期4-7,F0003,共5页China Modern Doctor

基　　金：辽宁省博士启动基金项目(20170520269)。

摘　　要：目的研究MAPK信号通路对结直肠癌SW480细胞MMP-9表达及细胞侵袭作用的影响。方法观察蛋白激酶C激活剂TPA诱导下SW480细胞形态学的改变;蛋白免疫印迹法检测MMP-9、P38MAPK蛋白的表达,zymography法检测MMP-9蛋白的分泌,利用Transwell实验观察细胞侵袭能力。结果显微镜下观察,随着TPA浓度的升高,细胞形态逐渐改变成针尖样;蛋白免疫印迹法显示,TPA处理下P38磷酸化增加,MMP-9蛋白表达和分泌增加,呈时间依赖性;并且肿瘤细胞侵袭能力随之增强;而通过预处理PKC抑制剂和P38抑制剂,可明显抑制TPA诱导的MMP-9表达和细胞侵袭能力。结论在结直肠癌SW480细胞中PKC激动剂TPA通过激活P38 MAPK信号通路调控MMP-9表达及细胞侵袭,为阻止结直肠癌侵袭转移研究提出多方位的作用靶点和新思路。Objective To study the effect of MAPK signaling pathway on the MMP-9 expression and cell invasion in colorectal cancer SW480 cells.Methods The morphological changes of SW480 cells induced by TPA,the activator of protein kinase C(PKC),were observed.Western blot method was adopted to detect the expression of MMP-9 and P38MAPK protein.Zymography was used to detect the secretion of MMP-9 protein.Transwell experiment was performed for the observation of cell invasion ability.Results Under microscope,with the increase of TPA concentration,the cell morphology gradually changed into pinpoint shape.Western blot method showed that after TPA treatment,the phosphorylation of P38 and the expression and secretion of MMP-9 protein increased in a time-dependent manner,and the tumor cell invasion ability was enhanced.However,the pretreatment of PKC inhibitor and P38 inhibitor can obviously inhibit the MMP-9 expression and cell invasion ability induced by TPA.Conclusion TPA,a PKC agonist,regulates and controls the MMP-9 expression and cell invasion through activating P38MAPK signaling pathway in colorectal cancer SW480 cells,which provides multi-directional targets and new ideas for the research on preventing the invasion and metastasis of colorectal cancer.

关 键 词：基质金属蛋白-9 促分裂原活化蛋白激酶P38 细胞侵袭 蛋白激酶C 结直肠癌 

分 类 号：R735.35[医药卫生—肿瘤]