夏枯草消瘤合剂联合安罗替尼抑制肺癌皮下移植瘤增殖的作用机制  

Mechanism of Xiakucao Xiaoliu Heji combined with Anlotinib in inhibiting subcutaneous tumor growth in lung cancer

作　　者：王芹 赵婧雯 何艺韵 赵蓓 李全耀 王程燕 杨文笑 周永明[1] WANG Qin;ZHAO Jingwen;HE Yiyun;ZHAO Bei;LI Quanyao;WANG Chengyan;YANG Wenxiao;ZHOU Yongming(Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200437,China;Technology Innovation Center,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Shanghai Jingan District Hospital of Traditional Chinese Medicine,Shanghai 200072,China)

机构地区：[1]上海中医药大学附属岳阳中西医结合医院,上海200437 [2]上海中医药大学科技创新中心,上海201203 [3]上海市静安区中医医院,上海200072

出　　处：《中华中医药杂志》2024年第7期3442-3447,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金青年科学基金项目(No.82104948,No.82205213);上海市卫生健康委员会卫生行业临床研究项目(No.20214Y0177)。

摘　　要：目的:探讨夏枯草消瘤合剂通过改变巨噬细胞M2转化途径增强安罗替尼对非小细胞肺癌(NSCLC)皮下移植瘤模型小鼠抑瘤的作用与机制。方法:24只SPF级雄性BALB/cNude裸小鼠随机分为生理盐水组、安罗替尼组、夏枯草消瘤合剂联合安罗替尼组,每组8只,皮下注射NCI-H1975细胞建立皮下移植瘤模型,造模成功后,各组灌胃给予相应药物。测量瘤体大小,采用转录组测序寻找差异基因,RT-qPCR法检测验证差异基因相关的巨噬细胞炎症因子mRNA表达水平。结果:与生理盐水组比较,夏枯草消瘤合剂联合安罗替尼组能显著抑制瘤体体积增长(P<0.05),且疗效优于安罗替尼组(P<0.05)。夏枯草消瘤合剂联合安罗替尼组及安罗替尼组治疗的抑瘤率分别为58.6%、43.4%。与安罗替尼组比较,夏枯草消瘤合剂联合安罗替尼组瘤体中检测到589个显著差异的基因,其中287个基因上调,302个基因下调,使用TIMER2.0利用IRIS数据库从RNA-seq数据中提取的免疫细胞表达特征,发现夏枯草消瘤合剂联合安罗替尼组与安罗替尼组主要差异免疫细胞为巨噬细胞比例增高。RT-qPCR验证显示,与生理盐水组、安罗替尼组比较,夏枯草消瘤合剂联合安罗替尼组能显著提高M1巨噬细胞相关CCL2、CCL3、IL-12、IL-1b促炎因子mRNA表达,下调M2相关抗炎细胞因子IL-10mRNA的表达(P<0.01)。结论:夏枯草消瘤合剂联合安罗替尼治疗能增强抑制NSCLC细胞皮下移植瘤增殖,其机制可能与促进M1表型巨噬细胞极化,M2表型巨噬细胞去极化有关。Objective:To investigate how the Xiakucao Xiaoliu Heji enhances the antitumor effects of Anlotinib in a subcutaneous tumor model of non-small cell lung cancer(NSCLC)by modulating the M2 macrophage transformation pathway.Methods:Twenty-four SPF male BALB/cNude mice were randomly divided into three groups:the saline group,the Anlotinib group,and the Xiakucao Xiaoliu Heji combined with Anlotinib group,with 8 mice in each group.Subcutaneous tumor models were established by injecting NCI-H1975 cells,and after successful modeling,each group was administered the corresponding drugs.Tumor size was measured,and differential genes were identified using transcriptome sequencing.The mRNA expression levels of macrophage infammatory factors related to differential genes were validated using RT-qPCR.Results:Compared with the saline group,the Xiakucao Xiaoliu Heji combined with Anlotinib group significantly inhibited tumor volume growth(P<0.05),and it was more effective than Anlotinib group(P<0.05).The tumor inhibition rates for the Xiakucao Xiaoliu Heji combined with Anlotinib group and Anlotinib group were 58.6%and 43.4%,respectively.Compared with the Anlotinib group,Xiakucao Xiaoliu Heji combined with Anlotinib group showed 589 significantly different genes in the tumor,with 287 upregulated genes and 302 downregulated genes.Using TIMER 2.0 and IRIS database,immune cell expression characteristics extracted from RNA-seq data revealed an increase in the proportion of macrophages in the Xiakucao Xiaoliu Heji combined with Anlotinib group compared to the Anlotinib group.RT-qPCR validation showed that the Xiakucao Xiaoliu Heji combined with Anlotinib group significantly increased the mRNA expression of pro-inflammatory factors related to M1 macrophages,such as CCL2,CCL3,IL-12,and ILIb,while downregulating the expression of anti-inflammatory factors related to M2 macrophages,such as IL-10 mRNA compared with the saline group and Anlotinib group(P<0.01).Conclusion:Combined treatment with the Xiakucao Xiaoliu Heji and Anlotinib enhance

关 键 词：夏枯草消瘤合剂 安罗替尼 巨噬细胞 抗血管生成 肺癌 皮下移植瘤模型 机制 非小细胞肺癌 

分 类 号：R734.2[医药卫生—肿瘤]