氧化苦参碱对小鼠肉瘤和肝癌的体内外抗肿瘤作用  

Anti-tumor effects of oxymatrine on mouse sarcoma and live cancers in vivo and in vitro

作　　者：刘宁 梁兰兰 李淑芳 沈祥春 梁冰[1] LIU Ning;LIANG Lanlan;LI Shufang;SHEN Xiangchun;LIANG Bing(Department of Pharmacology,School of Basic Medical Sciences,Guizhou Medical University,Guiyang 550025;The Key Laboratory of Optimal Utilization of Natural Medicine Resources,Guizhou Medical University,Guiyang 550025,Guizhou,China)

机构地区：[1]贵州医科大学基础医学院药理学教研室,贵州贵阳550025 [2]贵州医科大学天然药物优效利用重点实验室,贵州贵阳550025

出　　处：《癌变．畸变．突变》2021年第6期426-429,434,共5页Carcinogenesis,Teratogenesis & Mutagenesis

基　　金：贵州省高层次创新型人才百层次人才项目([2015]4029);贵州省高层次创新型人才千层次人才项目

摘　　要：目的:研究氧化苦参碱对小鼠肉瘤和肝癌的体内、外抗肿瘤作用,为氧化苦参碱在抗肿瘤方面的应用提供实验依据。方法:取对数生长期S_(180)和H_(22)细胞悬液预培养24 h,分别设立小鼠S180和H_(22)细胞的空白对照组(RPMI-1640培养基)、阴性对照组(不加药的S180和H_(22)细胞悬液)、5-氟尿嘧啶(5-FU,5×10^(-5)g/L)阳性对照组及5个不同浓度(1×10^(-4)、1×10^(-5)、1×10^(-6)、1×10^(-7)、1×10^(-8)g/L)的氧化苦参碱培养组,连续培养48 h后,采用四甲基噻唑蓝(MTT)法检测氧化苦参碱对S_(180)和H_(22)细胞的增殖抑制率。分别将S180和H_(22)瘤细胞悬液接种于昆明种小鼠,建立S_(180)和H_(22)荷瘤小鼠模型,分别设立正常对照组、模型组、阳性对照组、氧化苦参碱高、中、低剂量组,每组10只。正常对照组和模型组灌胃给予等体积蒸馏水,高、中、低剂量小鼠分别灌胃浓度为100、50、25 mg/kg的氧化苦参碱,阳性对照组灌胃给予30 mg/kg的环磷酰胺。各组连续给药8 d后,检测氧化苦参碱对S_(180)和H_(22)荷瘤小鼠的抑瘤率、胸腺系数和脾系数以及对S_(180)和H_(22)腹水瘤小鼠生存期的影响。结果:体外研究结果表明,与阴性对照组比较,氧化苦参碱对小鼠S_(180)和H_(22)细胞的增殖均有抑制作用(P<0.05)。动物实验表明,与模型组比较,氧化苦参碱100、50和25 mg/kg剂量组均能够显著抑制小鼠S180肉瘤的生长,抑瘤率分别为48.48%、41.67%和32.58%,差异具有统计学意义(P<0.05);氧化苦参碱100和50 mg/kg剂量组均能够显著抑制小鼠肝癌H_(22)的生长,抑瘤率分别为33.95%和31.63%,差异具有统计学意义(P<0.05);氧化苦参碱50 mg/kg剂量组可显著延长S180腹水型小鼠的生存期,其生命延长率为31.18%,差异具有统计学意义(P<0.05)。与正常对照组比较,氧化苦参碱各剂量组对S_(180)荷瘤小鼠和H_(22)荷瘤小鼠的胸腺系数和脾系数无明显影响(P>0.05)。结论:氧化苦参碱对�OBJECTIVE:To investigate anti-tumor effects of oxymatrine on S_(180)and H_(22)tumor bearing mice in vivo and in vitro,and to provide experimental basis for application of oxymatrine in treatment of cancers.METHODS:In vitro cell culture:S_(180)and H_(22)cell suspensions at logarithmic growth stage were precultured for 24 h.Mice S_(180)and H_(22)cells were divided into blank control group(RPMI-1640 medium),negative control group(un-supplemented S_(180)and H_(22)cell suspension),5-fluorouracil(5-FU,5×10^(-5)g/L)positive control group and 5 different concentrations of oxymatrine(1×10^(-4),1×10^(-5),1×10^(-6),1×10^(-7),1×10^(-8)g/L).After 48h of continuous culture,proliferation inhibition rates of oxymatrine on S_(180)and H_(22)cells were detected by tetramethylthiazolyl blue(MTT)method.In vitro animal experiments using our S_(180)and H_(22)tumor-bearing mouse models were:normal control group,model group,positive control group,and oxymatrine high-dose,mediumdose and low-dose groups were set up respectively,with 10 mice in each group.Normal control group and model group were intra-gastrically fed with distilled water,high,medium and low dose mice were intragastrically fed with oxymatrine at different concentrations(100,50 and 25 mg/kg),and positive control group was intra-gastrically fed with cyclophosphamide at 30 mg/kg.After 8 days of continuous administration,the inhibitory rate,thymus coefficient and spleen coefficient of oxymatrine on S_(180)and H_(22)tumor bearing mice and the survival of S_(180)and H_(22)ascites tumor mice were detected.RESULTS:Our results showed that oxymatrine inhibited proliferation of S_(180)and H_(22)cells in vitro as detected with the MTT method.Results from our in vivo studies showed that oxymatrine high,medium and low dose group significantly inhibited growth of S_(180)sarcoma in mice,and the tumor inhibition rate were 48.48%,41.67%and 32.58%respectively;oxymatrine high and medium dose group significantly inhibited the growth of H_(22)sarcoma in mice,and the tumor inhibition rate w

关 键 词：氧化苦参碱 抗肿瘤 S_(180) H_(22) 小鼠 

分 类 号：R730.1[医药卫生—肿瘤]