双参散结方联合替莫唑胺对胶质母细胞瘤小鼠髓源性抑制细胞的抑制作用及机制  

Inhibitory effects and mechanism of Shuangshen Sanjie Formula combined with temozolomide on myeloid-derived suppressor cells in mice with glioblastoma

作　　者：程孟祺 孙天恒 秦英刚[2] 花宝金[2] CHENG Mengqi;SUN Tianheng;QIN Yinggang;HUA Baojin(Department of Oncology,The First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Traditional Chinese Medicine),Hangzhou 310006,China;Department of Oncology,Guang'anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China)

机构地区：[1]浙江中医药大学附属第一医院(浙江省中医院)肿瘤内科,杭州310006 [2]中国中医科学院广安门医院肿瘤科,北京100053

出　　处：《中华中医药杂志》2025年第2期599-604,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：中国中医科学院科技创新工程项目(No.CI2021A01821);中国中医科学院科技创新工程创新团队(No.CI2021B009);中国中医科学院广安门医院所级课题(No.2019S452);国家中医药管理局中医药创新团队及人才支持计划项目(No.ZYYCXTD-C-202205)。

摘　　要：目的:观察双参散结方(SSF)联合替莫唑胺(TMZ)抑制U87MG胶质母细胞瘤的有效性及其对髓源性抑制细胞(MDSCs)的影响,并探索其机制。方法:建立荷U87MG胶质母细胞瘤小鼠模型,随机分为模型组、TMZ组、SSF+TMZ组,另取正常小鼠设空白组,给药干预后,观察小鼠移植瘤瘤重与体积,脾脏及肿瘤组织中MDSCs比例,磁珠分选小鼠脾脏MDSCs,Western Blot检测PTEN、PI3K、Akt蛋白表达水平。结果:TMZ组、SSF+TMZ组小鼠移植瘤瘤重、体积均显著小于模型组(P<0.01),且SSF+TMZ组显著低于TMZ组(P<0.05)。与空白组比较,模型组小鼠脾脏中MDSCs比例显著上升(P<0.01);与模型组比较,TMZ组及SSF+TMZ组小鼠脾脏中MDSCs比例,肿瘤组织内CD11b~+Ly6C~+单核细胞型、CD11b~+Ly6G~+粒细胞型MDSCs亚群比例,脾脏MDSCs中PI3K、Akt、p-Akt蛋白表达均显著下降(P<0.01),且SSF+TMZ组显著低于TMZ组(P<0.01,P<0.05),脾脏MDSCs中PTEN蛋白表达显著升高(P<0.01),且SSF+TMZ组显著高于TMZ组(P<0.01)。结论:双参散结方联合替莫唑胺可抑制U87MG胶质母细胞瘤生长,抑制脾脏MDSCs扩增,降低肿瘤微环境中MDSCs浸润程度,其机制可能与调节PTEN/PI3K/Akt通路相关。Objective:To observe the effectiveness of Shuangshen Sanjie Formula(SSF)combined with temozolomide(TMZ)in inhibiting U87MG glioblastoma and its effect on myeloid-derived suppressor cells(MDSCs),and explore its mechanism.Methods:A mouse model bearing U87MG glioblastoma was established and randomly divided into model group,TMZ group and SSF+TMZ group.Normal mice were taken as a blank group.After drug intervention,the weight and volume of the transplanted tumor in mice,the proportion of MDSCs in spleen and tumor tissue were observed.MDSCs in spleen of mice were sorted with magnetic beads,and the expression level of PTEN,PI3K,Akt protein was detected by Western Blot.Results:The tumor weight and volume of transplanted tumor in mice in TMZ group and SSF+TMZ group were significantly smaller than those in model group(P<0.01),and SSF+TMZ group was significantly lower than TMZ group(P<0.05).Compared with the blank group,the proportion of MDSCs in the spleen of mice in the model group increased significantly(P<0.01).Compared with the model group,the proportion of spleen MDSCs and the proportion of CD11b*Ly6C*monocyte and CD11b*Ly6G*granulocyte MDSCs subsets in tumor tissue as well as the expression of PI3K,Akt,p-Akt proteins in spleen MDSCs of mice in the TMZ group and SSF+TMZ group were significantly lower(P<0.01),and the SSF+TMZ group was significantly lower than the TMZ group(P<0.01,P<0.05),while the PTEN protein expression in spleen MDSCs was significantly increased(P<0.01),and the SSF+TMZ group was significantly higher than the TMZ group(P<0.01).Conclusion:SSF combined with TMZ can inhibit the growth of U87MG glioblastoma,inhibit the expansion of spleen MDSCs,and reduce the infiltration of MDSCs in the tumor microenvironment.The mechanism may be related to the regulation of PTEN/PI3K/Aktpathway.

关 键 词：胶质母细胞瘤 双参散结方 替莫唑胺 髓源性抑制细胞 U87MG细胞 

分 类 号：R285.5[医药卫生—中药学]