基于IL-6/JAK2/STAT3通路探讨加味三物白散对胃癌裸鼠移植瘤上皮间质转化的抑制作用
Study of Jiawei Sanwu Bai Powder in inhibiting epithelial-mesenchymal transition of gastric cancer in nude mice based on IL-6/JAK2/STAT3 pathway
刘芸 1孙相如 2朱莹3
作者信息
- 1. 湖南中医药大学,长沙 410208;湖南中医药大学第一附属医院,长沙 410008
- 2. 湖南中医药大学,长沙 410208
- 3. 湖南中医药大学第一附属医院,长沙 410008
- 折叠
摘要
目的:研究加味三物白散对胃癌裸鼠移植瘤上皮间质转化(EMT)的抑制作用及与白细胞介素-6(IL-6)/非受体型酪氨酸蛋白激酶2(JAK2)/信号转导及转录激活蛋白3(STAT3)通路的关系.方法:40只裸鼠随机分成模型组、加味三物白散组、阳性药物组、联合组,每组10只.造模、灌胃干预后,ELISA检测裸鼠血清IL-6、肿瘤坏死因子-α(TNF-α)、CEA、CA199含量,HE染色观察瘤组织病理改变,RT-PCR及Western Blot检测EMT及IL-6/JAK2/STAT3通路相关mRNA、蛋白表达情况.结果:与模型组比较,各给药组第12-18天瘤体体积显著缩小(P＜0.05),镜下肿瘤细胞有坏死区,血清中IL-6、TNF-α、CEA、CA199含量显著降低(P＜0.05),瘤组织中JAK2、STAT3、N-cadherin、Vimentin mRNA及STAT3、N-cadherin、Vimentin蛋白表达显著降低(P＜0.01,P＜0.05),E-cadherin mRNA及蛋白表达显著增加(P＜0.01,P＜0.05);且联合组各mRNA表达效果优于两单给药组(P＜0.05).结论:加味三物白散可通过调控IL-6/JAK2/STAT3信号通路抑制胃癌裸鼠移植瘤EMT,效果以联合用药为优.
Abstract
Objective:To study the inhibitory effect of Jiawei Sanwu Bai Powder on the epithelial-mesenchymal transition(EMT)of gastric cancer xenografts in nude mice and its correlation with the IL-6/JAK2/STAT3 pathway.Methods:Forty nude mice were randomly divided into a model group,Jiawei Sanwu Bai Powder group,a positive drug group,and a combination drug group,with 10 mice in each group.After modeling and gavage intervention,ELISA was used to detect serum IL-6,TNF-α,CEA and CA199 in nude mice,HE staining was used to observe pathological changes in tumor tissue,RT-PCR and Western Blot methods were used to detect the expression of EMT and IL-6/JAK2/STAT3 pathway related mRNA and proteins.Results:Compared with the model group,the tumor volume of each treatment group was significantly reduced(P＜0.05),and there were necrotic areas of tumor cells under microscope in each treatment group,the expression of IL-6,TNF-α,CEA and CA199 in the blood serum of nude mice was reduced(P＜0.05),and the mRNA expression of JAK2,STAT3,N-cadherin and Vimentin and the protein expression of STAT3,N-cadherin,Vimentin in tumor tissue were significantly reduced(P＜0.01,P＜0.05),while the mRNA and protein expression of E-cadherin were significantly increased(P＜0.01,P＜0.05),and the combined group had better efficacy in the five mRNA expression than the two single dose groups(P＜0.05).Conclusion:Jiawei Sanwu Bai Powder may regulate the IL-6/JAK2/STAT3 pathway to inhibit EMT in gastric cancer xenografts in nude mice,and its combination with 5-Fu exhibits a synergistic effect.
关键词
胃癌/加味三物白散/5-氟尿嘧啶/白细胞介素-6/非受体型酪氨酸蛋白激酶2/信号转导及转录激活蛋白3信号通路/上皮间质转化/机制Key words
Gastric cancer/Jiawei Sanwu Bai Powder/5-fluorouracil(5-Fu)/IL-6/JAK2/STAT3 pathway/Epithelial-mesenchymal transition(EMT)/Mechanism引用本文复制引用
基金项目
湖南省研究生创新科研项目(CX20220801)
湖南省中医药科研计划项目(R2023042)
出版年
2024
NETL
NSTL
万方数据