天葵子总生物碱对小鼠S180实体瘤的抑制作用及对肿瘤炎性微环境干预作用研究  

Inhibitory effect of total alkaloids from Semiaquilegia adoxoides(DC.)Makino on S180 and interventional effects on tumor inflammatory microenvironment

作　　者：孙建 王建农[1] SUN Jian;WANG Jian-nong(Institute of Basic Medicine,Xiyuan Hospital of China Academy of Chinese Medical Sciences,Beijing 100091)

机构地区：[1]中国中医科学院西苑医院基础医学研究所,北京100091

出　　处：《中南药学》2020年第6期959-962,共4页Central South Pharmacy

摘　　要：目的探讨不同浓度天葵子(TKZ)总生物碱对小鼠S180实体瘤的抑制作用以及对肿瘤相关巨噬细胞炎性因子表达的影响。方法取昆明种小鼠50只,建立S180实体瘤小鼠模型。造模次日将小鼠随机分为模型组,环磷酰胺组[0.02 g/(kg·d),ip],TKZ总生物碱高、中、低剂量组[分别为200、100、50 g/(kg·d),ig],肿瘤模型组小鼠灌胃等体积生理盐水,每日1次,连续10 d。观察并测定各组小鼠体质量、脏器(脾、胸腺)指数、肿瘤抑制率。ELISA法检测不同浓度的TKZ总生物碱对体外肿瘤相关巨噬细胞中炎性因子表达的影响。细胞实验分为空白对照组与给药组,天葵子总生物碱给药浓度分别为7.5、15、30、60μg·mL^-1,给药处理时间分别为0、24、36、48 h,阳性药为紫杉醇。测定不同处理时间下对肿瘤相关巨噬细胞中TGF-β、TNF-α、IL-6表达的影响。结果动物实验结果表明,与模型组比较,TKZ高、中剂量组瘤重均有下降,胸腺指数明显增加。细胞实验结果表明,与空白组相比,培养24 h后,60μg·mL^-1组可以显著促进TGF-β的分泌(P<0.01);培养24 h时,7.5μg·mL^-1组可以显著降低TNF-α的分泌(P<0.01);在24 h后各给药组中IL-6含量均明显降低(P<0.01)。结论TKZ总生物碱对小鼠S180实体瘤有显著抑制作用,且对小鼠免疫器官无影响。体外实验表明TKZ总生物碱抗肿瘤作用可能与影响相关炎性因子的分泌,调节肿瘤炎性微环境有关。Objective To investigate the inhibitory effect of total alkaloids from Semiaquilegia adoxoides(DC.)Makino on S180 solid tumors in mice and the expression of tumor-associated macrophage inflammatory factors at different doses.Methods Fifty KM mice were selected to establish S180 solid tumor mouse model.The mice were randomly divided into a model group(normal saline,ig),a cyclophosphamide group[0.02 g/(kg·d),ip],TKZ high,medium and low dose group[200,100,and 50 g/(kg·d),ig].The mice were administered once daily for 10 days.The body weight,organ(spleen,thymus)index and tumor suppression rate of mice in each group were observed.ELISA was used to detect the effects of different concentrations of TKZ on the expression of inflammatory factors in TAMs.The experiment was divided into a blank control group and 3 drug-administration groups,with drug concentrations of 7.5,15,30 and 60μg·mL^-1,and treated with 0,24,36,and 48 h.The positive control drug was paclitaxel.Results The mouse experiments showed that compared with the model group,the tumor mass of each administration group was reduced,while the spleen index and thymus index were increased.The cell experiments showed that after 24 h culturing,the 60μg·mL^-1 group significantly promoted the secretion of TGF-β(P<0.01);at 24 h,the 7.5μg·mL^-1 group significantly reduced TNF-αsecretion(P<0.01 compared with that of the blank group);the IL-6 content in each administration group was significantly lower than that of the blank control group(P<0.01)after 24 h.Conclusion TKZ total alkaloids have a significant inhibitory effect on S180 in mice,without affecting the mouse immune organs.In vitro experiments show that the anti-tumor effect of TKZ total alkaloids may be related to affecting the secretion of related inflammatory factors and regulatingtumor inflammatory microenvironment.

关 键 词：S180实体瘤 肿瘤相关巨噬细胞 炎性微环境 天葵子 生物碱 

分 类 号：R285.5[医药卫生—中药学]