摘要
目的:评估重楼皂苷Ⅶ干预MDSCs介导转移前微环境形成的作用,揭示"正虚伏毒"转移核心病机的生物学基础。方法:在C57BL/6小鼠上建立皮下移植瘤模型,随机分为4组,分别为生理盐水对照组(NS)、重楼皂苷Ⅶ组(PP7)、紫杉醇组(PTX)、重楼皂苷Ⅶ联合紫杉醇组(PP7+PTX),每组8只,每周给药3次,共用药两周。活体成像检测小鼠成瘤情况,流式细胞术检测外周血MDSCs表达,免疫组化检测MDSCs分泌的相关细胞因子和转移前微环境形成情况。结果:与对照组相比,PP7+PTX组与PP7组均可以控制瘤重(P<0.05),且PP7+PTX组在控制瘤体积方面具有显著性差异(P<0.001);小鼠体重方面无显著性差异;外周血中MDSCs的比例无显著性差异;免疫组化显示,与对照组相比,PP7、PTX、PP7+PTX组均可以下调IDO表达(P<0.01),而PP7+PTX组可下调Arg-1的表达(P<0.05);在转移前微环境方面,免疫组化检测显示,与对照组相比,PP7、PTX、PP7+PTX组均可以下调转移前微环境形成指标S100A8(P<0.05),但对S100A9无显著性差异。结论:重楼皂苷Ⅶ可抑制小鼠皮下瘤生长,并下调S100A8抑制转移前微环境形成,揭示重楼皂苷Ⅶ可能具有扶正的作用,但是否通过调控MDSCs发挥作用尚待进一步探索。
Objective:To evaluate the effect of polyphyllinⅦon the intervention of MDSCs-mediated premetastasic niche,which aims to reveal the biological basis of the core pathogenesis of"hidden toxicity due to vital qi deficiency"in cancer metastasis.Methods:C57 BL/6 mice were used to establish a subcutaneous tumor model and randomly divided into 4 groups,namely the normal saline control group(NS),the saponinsⅦgroup(PP7),the paclitaxel group(PTX),the saponinsⅦcombined with paclitaxel Group(PP7+PTX),each group of eight,give medicine three times a week,a total of two weeks,and continued administration for two weeks.We detected tumor formation through in vivo imaging,and detected the expression of MDSCs in peripheral blood by flow cytometry,and detected related cytokines secreted by MDSCs and the formation of pre-metastasic niche by immunohistochemistry(IHC).Results:Compared with NS group,both the PP7+PTX group and the PP7 group can control the tumor weight(P<0.05),and PP7+PTX group showed significant differences in tumor volume control(P<0.001);no significant difference was found in mouse body weight and the proportion of MDSCs in peripheral blood;IHC showed that compared with the normal saline group,the PP7,PTX,PP7+PTX group can down-regulate the expression of IDO(P<0.01),while the PP7+PTX group can also down-regulate the expression of Arg-1(P<0.05).In terms of Pre-metastasis niche,IHC results showed that the PP7,PTX,and PP7+PTX groups can down-regulate S100 A8(P<0.05)compared with the NS group,but there is no significant difference to S100 A9.Conclusion:PolyphyllinⅦinhibits growth of subcutaneous tumors and the formation of premetastasic niche by down-regulating S100 A8,but whether it regulates the immunosuppressive effect of MDSCs remains to be explored.
作者
罗斌
姚望
阙祖俊
于盼
罗添乐
田建辉(指导)
LUO Bin;YAO Wang;QUE Zu-Jun;YU Pan;LUO Tian-Le;TIAN Jian-Hui(Department of Oncology,Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2021年第4期454-458,462,共6页
Chinese Journal of Immunology
基金
国家自然科学基金上项目(No.81803777,81973517)
上海市科技英才扬帆计划项目(No.20YF1449900)资助
关键词
重楼皂苷Ⅶ
转移前微环境
髓源性抑制细胞
S100A8/9
正虚伏毒
PolyphyllinⅦ
Pre-metastasic niche
Myeloid-derived suppressor cells
S100A8/9
Deficiency of vital qi and hidden toxin
