槲皮苷通过调控转化生长因子-β/smads信号通路抑制结肠癌细胞迁移与侵袭  

Effect of quercitrin on migration and invasion of colon cancer by transforming growth factor beta/samds signal pathway

作　　者：李丹[1] 张宏博[2] 郝旭雯[3] 徐新生[4] Li Dan;Zhang Hongbo;Hao Xuwen;Xu Xinsheng(Department of Traditional Chinese Medicine,Tianjin Medical University General Hospital,Tianjin 300052,China;Department of Oncology,Nankai Hospital,Tianjin 300102,China;Department of Gastroenterology,Nankai Hospital,Tianjin 300102,China;Department of Surgery,Nankai Hospital,Tianjin 300102,China)

机构地区：[1]天津医科大学总医院中医科,天津300052 [2]天津市南开医院肿瘤科,天津300102 [3]天津市南开医院消化科,天津300102 [4]天津市南开医院外四科,天津300102

出　　处：《中华实验外科杂志》2024年第7期1494-1497,共4页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金(82074213、82274253,82204988)。

摘　　要：目的探讨槲皮苷通过调控转化生长因子-β1(TGF-β1)/smads信号通路抑制结肠癌细胞迁移与侵袭。方法 HCT116结肠癌细胞分为对照组、槲皮苷低、中、高剂量组, 分别使用0、5、10、20 μmol/L槲皮苷处理48 h, 噻唑蓝(MTT)实验检测细胞活力, 迁移实验检测细胞迁移能力, Transwell实验检测细胞侵袭能力, 蛋白质印迹法(Western blot)检测基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶抑制剂-1(TIMP-1)、波形蛋白(Vimentin)、E-钙黏蛋白(E-cadherin)、TGF-β1、p-Smad2及p-Samd3蛋白表达, 采用F检验分析组间差异。结果槲皮苷低、中、高剂量组细胞活力(0.48±0.01、0.41±0.01、0.34±0.01比0.54±0.02, F=26.354, P<0.05)、细胞迁移数目[(117.62±3.49)、(43.36±2.53)、(35.56±1.32)个比(176.48±9.35)个, F=35.624, P<0.05]、细胞侵袭数目[(86.31±3.83)、(41.28±2.26)、(30.41±1.26)个比(182.43±9.21)个, F=36.520, P<0.05]、MMP-9 (0.98±0.05、0.46±0.02、0.32±0.01比0.35±0.01, F=26.546, P<0.05)、Vimentin (0.53±0.03、0.41±0.03、0.20±0.01比0.08±0.00、F=27.649, P<0.05)、TGF-β1(0.82±0.05、0.74±0.04、0.70±0.04比0.35±0.01, F=30.325, P<0.05)、p-Smad2(1.78±0.09、1.56±0.10、0.84±0.05比0.41±0.03, F=33.654, P<0.05)及p-Smad3蛋白表达量(1.94±0.12、0.87±0.07、0.56±0.04比0.28±0.01, F=35.674, P<0.05)低于对照组, 槲皮苷低、中、高剂量组中TIMP-1(0.21±0.01、0.31±0.02、0.46±0.03比0.64±0.04, F=28.413, P<0.05)、E-cadherin蛋白表达量(0.09±0.00、0.22±0.01、0.43±0.02比0.89±0.07, F=28.561, P<0.05)高于对照组。结论槲皮苷能抑制HCT116细胞迁移及侵袭, 可能与抑制TGF-β1/smad2/3信号通路有关。Objective To explore the effect of quercitrin on migration and invasion of colon cancer by modulating transforming growth factor betal(TGF-β1)/samds signal pathway.Methods HCT116 co-lon cancer cells were divided into control group,low-,medium-,and high-dose quercetin groups,and trea-ted with 0,5,10,and 20μmol/L quercetin for 48 h,respectively.Cell viability was measured by methyl thiazolyl tetrazolium(MTT)assay.Cell migration ability was detected by migration test.Cell invasion abil-ity was detected by Transwell test.The expression of matrix metalloproteinase-9(MMP-9),tissue inhibitor of metalloproteinase-1(TIMP-1),Vimentin,E-cadherin,TGF-β1,p-Smad2 and p-Smad3 was detected by Western blotting.Inter group differences were analyzed by F-test.Results Cell viability(0.48±0.01,0.41±0.01,0.34±0.01 vs.0.54±0.02,F=26.354,P<0.05),the number of migrating cells[(117.62±3.49),(43.36±2.53),(35.56±1.32)vs.(176.48±9.35)F=35.624,P<0.05],the number of invasive cells[(86.31±3.83),(41.28±2.26),(30.41±1.26)vs.(182.43±9.21),F=36.520,P<0.05],the expression of MMP-9(0.98±0.05,0.46±0.02,0.32±0.01 vs.0.35±0.01,F=26.546,P<0.05),Vimentin(0.53±0.03,0.41±0.03,0.20±0.01 vs.0.08±0.00,F=27.649,P<0.05),TGF-β1(0.82±0.05,0.74±0.04,0.70±0.04vs.0.35±0.01,F=30.325,P<0.05),p-Smad2(1.78±0.09,1.56±0.10,0.84±0.05 vs.0.41±0.03,F=33.654,P<0.05)andp-Smad3(1.94±0.12,0.87±0.07,0.56±0.04 vs.0.28±0.01,F=35.674,P<0.05)protein in low-,medium-,and high-dose quercetin groups were significantly reduced as compared with those in control group.The expression of TIMP-1(0.21±0.01,0.31±0.02,0.46±0.03 vs.0.64±0.04,F=28.413,P<0.05),E-cadherin(0.09±0.00,0.22±0.01,0.43±0.02 vs.0.89±0.07,F=28.561,P<0.05)protein in low-,medium-,and high-dose quercetin groups was higher than that in control group.Conclusion Quercitrin could inhibit migration and invasion of HCT116 colon cancer cells probably by suppressing the TGF-β1/smad2/3 signal pathway.

关 键 词：槲皮苷 结肠癌 迁移 侵袭 转化生长因子-β1/smads信号通路 

分 类 号：R285[医药卫生—中药学]