毛兰素通过Hedgehog信号通路调控结直肠癌HT29细胞的上皮间质转化和血管生成  

Erianin regulates epithelial-mesenchymal transformation and angiogenesis of colorectal cancer HT29 cells via the Hedgehog signal pathway

作　　者：张国[1] 张波[1] 马刚[1] 胡安祥[2] ZHANG Guo;ZHANG Bo;MA Gang;HU Anxiang(Department of Gastrointestinal Surgery,Tengzhou Central People's Hospital,Tengzhou 277599,Shandong,China;Department of OncologyⅡ,Tengzhou Central People's Hospital,Tengzhou 277599,Shandong,China)

机构地区：[1]滕州市中心人民医院胃肠外科,山东滕州277599 [2]滕州市中心人民医院肿瘤二科,山东滕州277599

出　　处：《中国肿瘤生物治疗杂志》2023年第8期689-694,共6页Chinese Journal of Cancer Biotherapy

摘　　要：目的:基于Hedgehog信号通路探讨石斛提取物毛兰素(erianin,ER)抑制结直肠癌HT29细胞上皮间质转化(EMT)和血管生成的作用机制。方法:将HT29细胞分为空白对照组、ER-L(25μg/mL)组、ER-M(50μg/mL)组、ER-H(75μg/mL)组、ER-H(75μg/mL)+PM(Hedgehog通路激活剂,1.5μmol/L)组。MTT法检测细胞增殖活力,克隆形成实验检测细胞克隆形成能力,划痕实验和Transwell实验检测细胞迁移与侵袭能力,血管拟态形成实验检测血管生成能力,WB法检测与EMT进程、Hedgehog信号通路和拟态血管生成相关蛋白质的表达。结果:HT29细胞增殖活性随着ER质量浓度的升高而逐渐降低(P<0.05);与空白对照组比较,ER各组细胞克隆形成率、迁移与侵袭能力、血管形成能力、间质标志蛋白(N-cadherin、vimentin)、血管生成相关蛋白(VEGF、VE-cadherin)及Hedgehog通路相关蛋白(SHH、GLI1、SMO、c-Myc)表达均显著下降(均P<0.05),上皮标志蛋白(Ecadherin)、Hedgehog通路中融合蛋白抑制剂(SUFU)蛋白表达均显著上升(均P<0.05);PM处理在一定程度上逆转了ER对于HT29细胞增殖、EMT和血管生成的抑制作用(均P<0.05)。结论:ER可以抑制结直肠癌HT29细胞的增殖、迁移与侵袭、EMT和血管生成,其机制可能与抑制Hedgehog信号通路激活有关。Objective:To investigate the mechanism of the inhibitory effects of dendrobium etract erianin(ER)on epithelial-mesenchymal transition(EMT)and angiogenesis of colorectal cancer HT29 cells based on the Hedgehog signal pathway.Methods:HT29 cells were separated into the blank control group,ER-L(25μg/mL)group,ER-M(50μg/mL)group,ER-H(75μg/mL)group,and ER-H(75μg/mL)+PM(Hedgehog pathway activator,1.5μmol/L)group.MTT assay was applied to detect cell proliferative viability;the clonogenic ability of cells was detected by clonogenic assay;the abilities of cell migration and invasion were detected by scratch test and Transwell test;vascular mimicry test was applied to detect the ability of angiogenesis;WB assay was applied to detect the expressionof proteins related to EMT processes.Hedgehog signaling pathways,and mimic angiogenesis.Results:The proliferative viability of HT29 cells decreased gradually with the increase of ER concentration(P<0.05).Compared with the control group,cell clone formation rate,migration and invasion abilities,angiogenesis ability,the expressions of interstitial marker proteins(N-cadherin,vimentin),angiogenesis related proteins(VEGF,VE-cadherin)and hedgehog pathway related proteins(SHH,GLI1,SMO,c-Myc)in the various ER groups decreased,and the expressions of both epithelial marker protein(E-cadherin)and suppressor of fused protein(SUFU)in hedgehog pathway increased(all P<0.05).ER-H+PM group,to some extent,reversed the inhibition of ER on HT29 cell proliferation,EMT and angiogenesis(all P<0.05).Conclusion:ER can inhibit the proliferation,migration and invasion,EMT and angiogenesis of colorectal cancer HT29 cells,and its mechanism may be related to the inhibition of the activation of the Hedgehog signal pathway.

关 键 词：毛兰素 结直肠癌 HT29细胞 上皮间质转化 HEDGEHOG信号通路 血管生成 

分 类 号：R735.3[医药卫生—肿瘤] R730.52[医药卫生—临床医学]