白桦脂醇对宫颈癌裸小鼠移植瘤的抑制作用  

Inhibitory effect of betulin on cervical cancer nude mice transplantation tumors

作　　者：黄姗[1] 万飞[1] 孙景环[2] 王建军[3] HUANG Shan;WAN Fei;SUN Jing-huan;WANG Jian-jun(School of Traditional Chinese Medicine,Chongqing Medical and Pharmaceutical College,Chonging,401331 China;Department of Science Education,Chongqing Jiangjin District Hospital of Traditional Chinese Medicine,Chonging,402260 China;Department of Orthopaedics,Chongqing Jiangjin District Hospital of Traditional Chinese Medicine,Chonging,402260 China)

机构地区：[1]重庆医药高等专科学校中医学院,重庆401331 [2]重庆市江津区中医院科教科,重庆402260 [3]重庆市江津区中医院骨科,重庆402260

出　　处：《中国临床药理学杂志》2020年第23期3930-3933,共4页The Chinese Journal of Clinical Pharmacology

基　　金：重庆市卫生健康委员会2019年市级中医药重点学科基金资助项目(针灸推拿学201843);重庆市卫计委2017年度中医药科技基金资助项目(201738);重庆医药高等专科学校创新研究群体基金资助项目(2019238,ygz2019401,ygz2019501)。

摘　　要：目的研究白桦脂醇对宫颈癌裸小鼠移植瘤的抑制作用及相关作用机制。方法用裸小鼠左侧腋窝外侧皮下接种Caski宫颈癌细胞的方法构建宫颈癌裸小鼠模型。将成功构建的宫颈癌裸小鼠随机分为模型组及低、中、高剂量实验组,各20只。低、中、高剂量实验组裸小鼠分别腹腔注射白桦脂醇50,100,200 mg·kg^-1,每天3次,模型组腹腔注射等量0.9%NaCl,连续干预7 d。测定抑瘤率及胸腺指数、脾指数;用苏木精-伊红(HE)染色观察裸小鼠肿瘤组织病理学特点;用TdT介导的脱氧尿嘧啶缺口末端标记(TUNEL)法检测肿瘤细胞的凋亡情况;用蛋白质印迹(Wb)法检测肿瘤组织巨噬细胞移动抑制因子(MIF)、血管内皮细胞生长因子-C(VEGF-C)、p53蛋白的表达水平。结果低、中、高剂量实验组裸小鼠抑瘤率分别为(7.94±4.32)%,(36.42±3.87)%,(61.22±4.76)%;模型组和低、中、高剂量实验组胸腺指数分别为(6.02±1.31),(13.22±0.89),(16.64±1.97),(20.03±2.73)mg·kg^-1;脾指数分别为(29.12±7.34),(36.24±9.56),(45.36±8.14),(53.26±10.11)mg·kg^-1。与低剂量实验组比较,中、高剂量实验组裸小鼠的抑瘤率升高,且高剂量实验组高于中剂量实验组;与模型组比较,低、中、高剂量实验组裸小鼠的胸腺指数、脾指数及肿瘤细胞的凋亡指数均升高;低、中、高剂量实验组裸小鼠肿瘤组织MIF、VEGF-C蛋白相对表达量均降低,p53蛋白相对表达量升高,且呈剂量依赖性(均P<0.05)。结论白桦脂醇可呈剂量依赖性地抑制宫颈癌裸小鼠移植瘤的生长,促进肿瘤细胞凋亡,同时改善免疫功能,发挥抗宫颈癌的作用,其作用机制可能与下调肿瘤组织MIF、VEGF-C蛋白表达,上调p53蛋白表达相关。Objective To investigate the inhibitory effect of betulin on cervical cancer nude mice transplantation tumor and its related mechanism.Methods The nude mice models of cervical cancer were constructed by subcutaneously inoculating Caski cervical cancer cells on the left lateral armpit of nude mice.The successfully constructed cervical cancer nude mice were randomly divided into model group and exp-L/M/H groups,with 20 nude mice in each group.The nude mice in exp-L/M/H groups were injected intraperitoneally with betulin 50,100,200 mg·kg^-1,3 times·d^-1,model group was injected intraperitoneally with the same amount of normal saline for 7 d.The tumor inhibition rate,thymus index and spleen index were measured;hematoxylin-eosin(HE)staining was used to observe the histopathological characteristics of nude mice tumors;TdT-mediated dUTP nick end labeling(TUNEL)method was used to detect tumor cell apoptosis;Western blotting(Wb)method was used to detect the expression levels of macrophage migration inhibitory factor(MIF),vascular endothelial growth factor-C(VEGF-C),and p53 protein in tumor tissues.Results The tumor inhibition rates of nude mice in exp-L/M/H groups were(7.94±4.32)%,(36.42±3.87)%,(61.22±4.76)%;the thymus indexes in model group and exp-L/M/H groups were(6.02±1.31),(13.22±0.89),(16.64±1.97),(20.03±2.73)mg·kg^-1;the spleen indexes were(29.12±7.34),(36.24±9.56),(45.36±8.14),(53.26±10.11)mg·kg^-1.Compared with exp-L group,the tumor inhibiting rate of nude mice in exp-M/H groups were increased,and exp-H group was higher than exp-M group;compared with model group,the thymus index,spleen index,and tumor cell apoptosis index of the nude mice in exp-L/M/H groups were increased;the relative expression levels of MIF and VEGF-C protein in the tumor tissue of nude mice in exp-L/M/H groups were decreased,while the relative expression levels of p53 protein was increased in a dose-dependent manner(all P<0.05).Conclusion Betulin can dose-dependently inhibit the growth of transplanted tumors in cervical cancer

关 键 词：宫颈癌 白桦脂醇 抑瘤率 巨噬细胞移动抑制因子 血管内皮细胞生长因子-C 

分 类 号：R28[医药卫生—中药学]