合江佛手挥发油靶向VEGF/VEGFR信号通路抗U87细胞肿瘤新生血管的生成  

Anti-angiogenesis by Volatile Oil of Citrus medica var.sarcodactylis from Hejiang on U87 Cells through the VEGF/VEGFR Signaling Pathway

作　　者：韩江云 陈晓霞 阳丽娟 刘睿涵 杨文娅 张丹 HAN Jiang-yun;CHEN Xiao-xia;YANG Li-juan;LIU Rui-han;YANG Wen-ya;ZHANG Dan(Affiliated Traditional Chinese Medicine Hospital,Southwest Medical University,Luzhou 646000,China;School of Pharmacy,Southwest Medical University,Luzhou 646000,China;Department of Clinical Medicine,Sichuan College of Traditional Chinese Medicine,Mianyang 621000,China)

机构地区：[1]西南医科大学附属中医医院,四川泸州646000 [2]西南医科大学药学院,四川泸州646000 [3]四川中医药高等专科学校临床医学系,四川绵阳621000

出　　处：《现代食品科技》2021年第8期36-43,共8页Modern Food Science and Technology

基　　金：四川省科技厅重点研发项目(2019YFS0116);合江县人民政府-西南医科大学科技专项项目(2018-HJXNYD-2);大学生创新创业项目(S201910808177X,S202010632121)。

摘　　要：本文研究合江佛手挥发油体外抗肿瘤活性及体内对裸鼠人神经胶质瘤U87细胞移植瘤血管生成的抑制作用。采用细胞增殖实验CCK-8法筛选合江佛手挥发油体外敏感的肿瘤细胞。皮下接种建立裸鼠U87细胞移植瘤模型,观察合江佛手挥发油(12.5、25、50 mg/kg)体内对裸鼠U87细胞移植瘤生长、MVD(微血管密度)和VEGF及其受体(flt-1、KDR)表达的影响。研究发现合江佛手挥发油对4株肿瘤细胞U87、MCF-7、A549、HepG2的IC50分别为82.19、173.99、215.83、192.87μg/mL,其中敏感性最强的是U87细胞。合江佛手挥发油灌胃给药后明显降低TV(肿瘤体积)、RTV(相对肿瘤体积)、T/C%(相对肿瘤增殖率),对裸鼠移植瘤的生长具有明显抑制作用;阳性对照及合江佛手挥发油治疗组肿瘤微血管稀疏分布,U87细胞MVD值由对照组的63.24分别降低到30.65、46.88、40.18、36.56。蛋白相对表达VEGF由对照组的0.93分别降低到0.19、0.52、0.33、0.16,flt-1由对照组的0.82分别降低到0.18、0.50、0.32、0.09,KDR由对照组的0.78分别降低到0.14、0.48、0.30、0.11。合江佛手挥发油具有一定的体外抗肿瘤性活性,特别是对U87细胞作用最敏感。体内抗神经胶质瘤的分子其机制可能与靶向抑制VEGF/VEGFR信号通路,抗肿瘤新生血管生成有关。To study the in vitro antitumor activity of the volatile oil of Citrus medica var.sarcodactylis from Hejiang and its anti-angiogenic effects on the transplanted human glioma cells U87 in nude mice,a CCK-8 assay was used to screen tumor cells sensitive to the volatile oil in vitro.Tumor models were established by transplanting the U87 cells to nude mice to observe the effects of volatile oil(at 12.5,25,and 50 mg/kg)on the tumor growth,microvessel density(MVD),expressions of vascular endothelial growth factors(VEGF),and expressions of the receptors VEGFRs(flt-1 and KDR)of the transplanted U87 cells in vivo.As the IC50 values of the volatile oil on four tumor cell lines,namely U87,MCF-7,A549,and HepG2 are 82.19μg/mL,173.99μg/mL 215.83μg/mL,and 192.87μg/mL,respectively,U87 cells are the most sensitive to the oil.After the oral administration of the volatile oil,the tumor volume(TV),relative TV,and relative tumor proliferation ratio decrease significantly;therefore,the volatile oil can significantly inhibit the growth of transplanted tumors in nude mice.The microvessel distribution of the volatile oil-treated group is sparse compared to that of the control.Meanwhile,the MVD value decreases from 63.24(control)to 30.65,46.88,40.18,and 36.56,whereas the relative expression of VEGF decreases from 0.93 to 0.19,0.52,0.33,and 0.16.The relative expression of flt-1 reduces from 0.82 to 0.18,0.50,0.32,and 0.09,whereas that of KDR reduces from 0.78 to 0.14,0.48,0.30,and 0.11.In short,the volatile oil exhibit significant in vitro antitumor activity,with its effects on U87 cells being the most evident.The in vivo antiglioma effects may be realized via the VEGF/VEGFR signaling pathway to achieve antiangiogenesis in tumors.

关 键 词：合江佛手挥发油 U87细胞 裸鼠 微血管密度 血管内皮生长因子 

分 类 号：R285[医药卫生—中药学]