仙连解毒方抑制结肠癌肝转移的作用及机制  

Effects and mechanism of Xianlian Jiedu Decoction on inhibiting liver metastasis of colon cancer

作　　者：范蓉 程海波 许惠琴[1] 沈卫星 孙东东 李柳[1,2] 徐长亮 赖岳阳[1] 余成涛 范旻旻[1,2] 谭佳妮 FAN Rong;CHENG Hai-bo;XU Hui-qin;SHEN Weixing;SUN Dong-dong;LI Liu;XU Chang-liang;LAI Yue-yang;YU Cheng-tao;FAN Min-min;TAN Jia-ni(Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor,Nanjing 210023,China;The First Clinical Medical College,Nanjing University of Chinese Medicine,Nanjing 210023,China;College of Traditional Chinese Medicine,College of Integrated Traditional Chinese and Western Medicine,Nanjing University of Chinese Medicine,Nanjing 210023,China)

机构地区：[1]江苏省中医药防治肿瘤协同创新中心,南京210023 [2]南京中医药大学第一临床医学院,南京210023 [3]南京中医药大学中医学院·中西医结合学院,南京210023

出　　处：《中华中医药杂志》2022年第9期5109-5113,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金重点项目(No.81930117);国家自然科学基金青年科学基金项目(No.81804073,No.81673559);江苏省高等学校自然科学研究项目(No.19KJB360011,No.22KJA360006);江苏高校优势学科建设工程资助项目(PAPD)。

摘　　要：目的:探讨仙连解毒方通过影响肿瘤相关巨噬细胞的分布抑制结直肠癌肝转移的作用及机制。方法:BALB/c小鼠通过脾脏注射结直肠癌细胞的方法建立脾脏肝转移模型,按体质量随机分组,连续给药21 d后处死小鼠,剥取小鼠肝脏组织,观察结直肠肿瘤肝转移情况。HE染色观察组织病理形态学变化;流式细胞仪检测小鼠外周血及腹腔灌洗液内F4/80~+CD11b~+肿瘤相关巨噬细胞分布情况;Western blot检测肝组织内JAK2、STAT3、p-JAK2、p-STAT3及MMP2、MMP9蛋白表达水平,免疫组化检测肝转移灶内F4/80~+巨噬细胞分布及MMP9蛋白表达。结果:与模型组比较,仙连解毒方具有显著抑制结直肠癌肝转移的作用(P<0.01),降低肿瘤相关巨噬细胞在外周血及腹腔的分布,减少肝转移灶内巨噬细胞的浸润,显著性降低肝转移灶内p-JAK2/AK2、p-STAT3/STAT3蛋白比值(P<0.01);同时显著性抑制MMP2、MMP9蛋白在肝转移灶内的表达(P<0.01)。结论:仙连解毒方具有显著抑制结直肠癌转移的作用,其机制可能与抑制JAK2-STAT3通路,下调MMP2、MMP9,减少肿瘤微环境中肿瘤相关巨噬细胞的浸润相关。Objective:To explore the effects and the possible mechanisms of Xianlian Jiedu Decoction on inhibiting liver metastases of colon cancer.Methods:CT26 cells were injected subcutaneously into the spleen of BALB/c mice to establish the colorectal cancer liver metastasis model.These mouse were randomly divided into groups according to body weight.After the mice were sacri?ced for 21 days,liver tissue was stripped to observe the intrahepatic metastasis of colorectal cancer.Histopathological changes were observed by HE staining;The distribution of F4/80CD11btumor associated macrophages (TAM)in peripheral blood and peritoneal lavage?uid of mice was detected by?ow cytometry;Western blot or immunohistochemical staining was used to detect the protein expression levels of JAK2,STAT3,p-JAK2,p-STAT3,MMP2 and MMP9 in liver tissues,Immunofluorescence was used to detect the distribution of macrophages in liver metastases.Results:Compared with model group,Xianlian Jiedu Decoction could signi?cantly inhibit the liver metastasis of colon cancer,reduce the distribution of TAM in peripheral blood and peritoneal lavage?uid,reduce the in?ltration of macrophages in liver metastasis (P<0.01),and reduce the expression of p-JAK2/JAK2,p-STAT3/STAT3,MMP2 and MMP9 in liver metastasis (P<0.01).Conclusion:Xianlian Jiedu Decoction can signi?cantly inhibit the metastasis of colon cancer.The mechanism is probably related to inhibiting JAK2/STAT3pathway,down regulating MMP2 and MMP9,reducing the in?ltration of TAM in the tumor microenvironment.

关 键 词：仙连解毒方 结肠癌 肿瘤相关巨噬细胞 JAK2/STAT3信号通路 

分 类 号：R285.5[医药卫生—中药学]