补骨脂素对人结肠癌细胞侵袭转移及β-catenin/TCF4-MMP-9信号通路的影响  

Effects of psoralen on invasion and metastasis of human colon cancer cells and β-catenin/TCF4-MMP-9 signaling pathway

作　　者：冯媛媛[1] 周利红[2] 刘宁宁[1] 孙筱婷 贾茹 李琦[1,2,3] FENG Yuan-yuan;ZHOU Li-hong;LIU Ning-ning;SUN Xiao-ting;JIA Ru;LI Qi(Department of Oncology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Cancer Institute,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Institute of Integrated Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属曙光医院肿瘤科,上海201203 [2]上海中医药大学附属曙光医院肿瘤研究所,上海201203 [3]上海中医药大学中西医结合研究院,上海201203

出　　处：《中华中医药杂志》2021年第12期7033-7037,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金青年科学基金项目(No.81703893)。

摘　　要：目的:探讨补骨脂素对人结肠癌细胞侵袭转移及对β-catenin、TCF4、VEGF、MMP-9表达水平的影响。方法:以不同浓度的补骨脂素分别作用于人结肠癌HCT-116细胞24、48、72h,CCK-8法检测补骨脂素对HCT-116细胞增殖率的影响;细胞划痕、Transwell实验检测补骨脂素对HCT-116细胞转移及侵袭能力的影响;Western Blot检测β连环蛋白(β-catenin)、转录因子4(TCF4)蛋白表达情况;ELISA检测补骨脂素对HCT-116细胞血管内皮生长因子(VEGF)及基质金属蛋白酶9(MMP-9)表达的影响。结果:CCK8实验显示补骨脂素对人结肠癌HCT-116细胞的增殖率有抑制作用,呈剂量-时间依赖关系,24、48、72h的IC_(50)分别为123.75、94.63、37.87μg/mL;划痕及Transwell实验表明,补骨脂素能显著抑制HCT-116细胞的转移与侵袭能力;补骨脂素能够下调人结肠癌HCT-116细胞核内β-catenin、TCF4蛋白表达水平及VEGF、MMP-9的表达水平(P<0.05,P<0.01)。结论:补骨脂素能够抑制人结肠癌HCT-116细胞侵袭转移,其机制可能与下调β-catenin、TCF4蛋白表达水平及其下游靶基因VEGF、MMP-9的表达水平相关。Objective: To investigate the effects of psoralen on the invasion and metastasis of human colon cancer cells and the expression levels of β-catenin, TCF4, VEGF and MMP-9. Methods: Psoralen at different concentrations was treated with human colon cancer HCT-116 cells for 24, 48 and 72 h, respectively. The proliferation rate of HCT-116 cells was detected by CCK-8 assay. The effect of psoralen on the migration and invasion ability of HCT-116 cells was detected by cell scratch and Transwell assay. The protein expression of β-catenin and TCF4 were detected by Western Blot. The expression of Psoralen on vascular endothelial growth factor(VEGF) and matrix metalloproteinase-9(MMP-9) in HCT-116 cells were detected by ELISA.Results: CCK8 assay showed that psoralen could inhibit the proliferation rate of human colon cancer HCT-116 cells in a dose-time dependent manner. The IC_(50) values at 24 h, 48 h and 72 h were 123.75, 94.63 and 37.87μg/mL, respectively. The scratch test and Transwell assay showed that psoralen could significantly inhibit the migration and invasion of HCT-116 cells. Psoralen can downregulate the protein expression levels of β-catenin and TCF4 in the nucleus of human colon cancer HCT-116 and the expression levels of VEGF and MMP-9(P<0.05, P<0.01). Conclusion: Psoralen can inhibit the invasion and metastasis of human colon cancer HCT-116 cells, and the mechanism may be related to the down-regulation of β-catenin and TCF4 protein expression as well as the downstream target genes VEGF and MMP-9 expression.

关 键 词：补骨脂素 大肠癌 信号通路 Β-连环蛋白 侵袭转移 

分 类 号：R285[医药卫生—中药学]