摘要
目的:基于ATF2和JAK2/STAT3信号通路研究麦门冬汤合千金苇茎汤联合顺铂对Lewis肺癌小鼠肿瘤生长的抑制作用及对免疫功能的影响。方法:建立C57BL/6小鼠Lewis肺癌模型,分别给予生理盐水、麦门冬汤合千金苇茎汤、顺铂、麦门冬汤合千金苇茎汤+顺铂,连续给药21 d后,剥取瘤体称量质量并计算抑瘤率,计算胸腺和脾脏指数,HE染色观察肿瘤组织病理学改变;流式细胞仪检测CD4^(+)T淋巴细胞(CD4^(+))、CD8^(+)T淋巴细胞(CD8^(+))的分布与比例;采用ELISA法测定血清TNF-α、IL-10、IL-12、IL-16含量;采用免疫组化法检测肿瘤组织中侵袭转移相关蛋白ATF2、MMP-2、MMP-9的表达;采用Western Blot检测肿瘤组织中JAK2/STAT3信号通路相关蛋白表达。结果:与模型组比较,各给药组瘤质量均显著降低(P<0.01)。与模型组比较,顺铂组小鼠胸腺及脾脏指数均有所降低,而麦门冬汤合千金苇茎汤组与麦门冬汤合千金苇茎汤+顺铂组的胸腺及脾脏指数显著升高(P<0.01),光镜下可见各给药组肿瘤组织坏死程度加大,分裂增殖程度减轻。与模型组比较,各给药组小鼠脾淋巴细胞亚群CD4^(+)/CD8^(+)比值显著升高,血清TNF-α、IL-10、IL-12、IL-16含量及瘤体组织中ATF2、MMP-2、MMP-9、p-JAK2、p-STAT3蛋白表达均显著降低(P<0.05或P<0.01)。结论:麦门冬汤合千金苇茎汤与顺铂单独和联合使用对Lewis肺癌小鼠模型均有显著的体内抗肿瘤作用,同时可增强机体的免疫功能,降低机体炎症水平,其机制可能与下调ATF2、MMP-2、MMP-9表达和干预JAK2/STAT3信号转导通路有关。
Objective:To study the effect of Maimendong decoction and Qianjinweijing decoction combined with cisplatin on tumor inhibition and immune function of mice with Lewis lung cancer based on ATF2 and JAK2/STAT3 signaling pathway.Methods:Lewis lung cancer model of C57BL/6 mice was established,and normal saline,Maimendong decoction and Qianjinweijing decoction,cisplatin,Maimendong decoction and Qianjinweijing decoction with cisplatin were given for 21 days.After continuous administration,the tumor bodies were exfoliated,the tumor weight and inhibitory rate were analyzed,and the thymus and spleen indexes were calculated.HE stai-ning was used to observe the histological changes of the tumor.Flow cytometry was used to detect the distribution and proportion of CD4^(+)T lymphocytes(CD4^(+))and CD8^(+)T lymphocytes(CD8^(+)).The contents of TNF-α,IL-10,IL-12 and IL-16 in serum were deter-mined by ELISA.The expressions of invasion and metastasis related proteins ATF2,MMP-2 and MMP-9 were detected by immunohisto-chemistry,and the expressions of JAK2/STAT3 signaling pathway related proteins in tumor tissues were detected by Western Blot.Results:Compared with model group,the tumor weight of all treatment groups was significantly decreased(P<0.01).Compared with model group,the indexes of thymus and spleen in cisplatin group were decreased,while the indexes of thymus and spleen in Maimen-dong decoction and Qianjinweijing decoction group and Maimendong decoction combined Qianjinweijing decoction with cisplatin group were significantly increased(P<0.01).The degree of necrosis of tumor tissue was increased and the degree of division and proliferation was reduced under light microscope in each drug group.Compared with model group,the CD4^(+)/CD8^(+)ratio of splenic lymphocyte sub-sets of mice in each drug group was significantly increased,and the contents of TNF-α,IL-10,IL-12 and IL-16 in serum and the protein expressions of ATF2,MMP-2,MMP-9,p-JAK2 and p-STAT3 in the tumor were significantly decreased(P<0.05 or P<0.01).Conclu-sion:Ma
作者
孙莎莎
谢美萍
孙玉侠
李文婷
吴勉华
姜海英
姜泽群
SUN Sha-sha;XIE Mei-ping;SUN Yu-xia;LI Wen-ting;WU Mian-hua;JIANG Hai-ying;JIANG Ze-qun(School of Medicine/School of Integrative Medicine,Nanjing University of Chinese Medicine,Nanjing 210023,China;Nanjing U-niversity of Chinese Medicine/Jiangsu Collaborative Innovation Center of TCM Prevention and Treatment of Cancer,Nanjing 210023,)
出处
《中药材》
CAS
北大核心
2023年第7期1753-1759,共7页
Journal of Chinese Medicinal Materials
基金
国家自然科学基金项目(81603584,81804058)
“十四五”江苏省重点学科-生物学资助项目(35091005006)
吴勉华全国名老中医药专家传承工作室(国中医药人教函[2022]75号)。
关键词
肺癌
麦门冬汤合千金苇茎汤
顺铂
激活转录因子2
Janus激酶2/转录激活因子3信号通路
Lung cancer
Maimendong decoction and Qianjinweijing decoction
Cisplatin
Activated transcription factor 2
Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway
