醉鱼草皂苷Ⅳ激活线粒体抑制αβ整合素在结直肠癌小鼠肝转移中的作用及机制研究  

The role and mechanism of Buddlejasaponin Ⅳ activated mitochondria to inhibit αβ integrin in liver metastasis of colorectal cancer

作　　者：房斌 范雪梅 毕宏伟 丁明辉[4] FANG Bin;FAN Xue-mei;BI Hong-wei;DING Ming-hui(Department of Gastrointestinal Surgery,Qingdao Hospital of Traditional Chinese Medicine,Qingdao Hiser Hospital,Qingdao 266000,Shandong Province,China;Department of Surgery,Qingdao Hospital of Traditional Chinese Medicine,Qingdao Hiser Hospital,Qingdao 266000,Shandong Province,China;Department of Pharmacy,Qingdao Hospital of Traditional Chinese Medicine,Qingdao Hiser Hospital,Qingdao 266000,Shandong Province,China;Department of Hepatobiliary Surgery,Qingdao Hospital,University of Health and Rehabilitation Sciences,Qingdao Municipal Hospital,Qingdao 26601l,Shandong Province,China)

机构地区：[1]青岛市中医医院、市海慈医院胃肠外科,山东青岛266000 [2]青岛市中医医院、市海慈医院外科,山东青岛266000 [3]青岛市中医医院、市海慈医院药剂科,山东青岛266000 [4]康复大学青岛医院、青岛市市立医院肝胆外科,山东青岛266011

出　　处：《中国临床药理学杂志》2023年第20期2965-2969,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的 探讨醉鱼草皂苷Ⅳ(BS-Ⅳ)激活线粒体抑制αβ整合素在结直肠癌的肝转移中的作用及机制。方法 将60只BALB/c小鼠分为对照组、模型组和低、中、高剂量实验组(0.1、1、2 mg·kg^(-1 )BS-Ⅳ),除对照组外其余4组小鼠通过尾静脉注射肠癌细胞建立结直肠癌小鼠模型,造模成功后干预2周。观察各组小鼠肝表面的肿瘤结节数量和肝质量。将HT-29细胞培养传代后用1、2、3、4、5、10μmol·L^(-1)BS-Ⅳ培养,检测各组细胞存活率、凋亡率及细胞黏附性,并用蛋白质印迹法检测细胞B淋巴细胞瘤-2(Bcl-2)和Bcl-2相关X(Bax)蛋白表达水平。结果 对照组、模型组与低、中、高剂量实验组小鼠的肿瘤结节数量分别为0、(12.33±1.58)、(8.26±0.73)、(5.14±0.91)、(3.33±0.28)个;肝质量分别为(1.63±0.13)、(5.58±0.64)、(4.89±0.51)、(3.74±0.57)、(2.26±0.28)g;模型组与对照组相比,低、中、高剂量实验组与模型组相比,差异均有统计学意义(均P<0.05)。经1、2、3、4、5、10μmol·L^(-1)的BS-Ⅳ处理后,HT-29结直肠癌细胞的细胞活性分别为(93.20±1.48)%、(78.02±2.33)%、(39.05±3.46)%、(19.10±4.03)%、(18.41±4.21)%、(18.31±4.98)%,随着剂量增加,HT-29结直肠癌细胞的细胞活性得到显著抑制(均P<0.05)。4、5、10μmol·L^(-1)BS-Ⅳ处理2 h后,HT-29结直肠癌细胞的细胞凋亡率分别为(12.20±1.48)%、(23.02±2.13)%、(37.85±2.56)%;0、4、5、10μmol·L^(-1)BS-Ⅳ组HT-29细胞的黏附细胞数量分别为(18.13±0.46)×10~5、(14.02±0.34)×10~5、(8.09±0.21)×10~5、(2.98±0.08)×10~5,与0μmol·L^(-1) BS-Ⅳ组HT-29细胞相比,BS-Ⅳ干预后HT-29细胞的黏附细胞数量减少(均P<0.01)。HT-29细胞经BS-Ⅳ处理后,α_(2)β_1整合素的表达水平显著下降,对Ⅰ型和Ⅳ型胶原蛋白的黏附力明显下降,与经BS-Ⅳ处理的细胞相比,差异均有统计学意义(均P<0.05)。结论 醉鱼草皂苷Ⅳ可能通过激活线粒体抑制αβ整合素,有效抑制结直�ObjectiveTo investigate the inhibitory effect o mitochondria activated by BuddlejasaponinⅣ(BS-Ⅳ) on αβ integrin in liver metastasis of colorectal cancer and its mechanism.Methods Sixty BALB/c mice were divided into control group,model group and experimental-L,-M,-H groups (0.1,1,2 mg·kg^(-1)BS-Ⅳ).Except for the control group,the other groups of mice were injected with intestinal cancer cells through the tail vein to establish model of colorecta cancer.After successful modeling,the intervention lasted for two weeks.The number of tumor nodules and the weight of liver were observed.After HT-29 cells were cultured and passaged,they were divided into control,model and experimental groups (1,2,3,4,5,10μmol·L^(-1)),and the cell survival rate,apoptosis rate and cell adhesion assay were measured in each group,the effect of Bcl-2-associated X protein(Bax) and B-cell lymphoma-2 (Bcl-2) protein expression was detected by Western blotting.Results The number of tumor nodules in control group,model group and experimental-L,-M,-H groups were 0,12.33±1.58,8.26±0.73,5.14±0.91 and 3.33±0.28;liver weight were (1.63±0.13),(5.58±0.64),(4.89±0.51),(3.74±0.57),(2.26±0.28) g.Compared between model group and control group,compared between experimental-L,-M,-H groups and model group,the difference were statistically significant (all P0.05).After BS-Ⅳtreatment with 1,2,3,4,5 and 10μmol·L^(-1),the cell activity of HT-29 colorectal cancer cells were (93.20±1.48)%,(78.02±2.33)%,(39.05±3.46)%,(19.10±4.03)%,(18.41±4.21)%,(18.31±4.98)%,the cell activity of HT-29 colorectal cancer cells was significantly inhibited (P0.05).After being treated with 4,5 and 10μmol·L^(-1)BS-Ⅳfor 2 hours,the apoptosis rates of HT-29 colorectal cancer cells were (12.20±1.48)%,(23.02±2.13)%,(37.85±2.56)%.After 0,4,5 and 10μmol·L^(-1)BS-Ⅳtreatment,the number of adherent cells of HT-29 cells were (18.13±0.46)×10~5,(14.02±0.34)×10~5,(8.09±0.21)×10~5,(2.98±0.08)×10~5,compared with untreated HT-29 cells,the number of adherents

关 键 词：醉鱼草皂苷Ⅳ 线粒体 αβ整合素 结直肠癌 肝转移 

分 类 号：R28[医药卫生—中药学]