中医药导报2025，Vol.31Issue(12)：14-19,6.DOI:10.13862/j.cn43-1446/r.2025.12.003
补中益气加味方对裸鼠结直肠癌移植瘤Klotho蛋白及Caspase-1、IL-1β、IL-18表达的影响
Study on the Effects of Modified Buzhong Yiqi Formula(补中益气加味方)on the Expression of Klotho and Caspase-1,IL-1β and IL-18 in Transplanted Colon Cancer Tumors of Nude Mice
摘要
Abstract
Objective:To explore the mechanism of action of the modified Buzhong Yiqi formula in inhibiting the growth of colorectal cancer xenografts by regulating Klotho protein and pyroptosis.Methods:A nude mouse xenograft model was established using HCT116 human colorectal cancer cells.After 15 days of model establishment,the mice were randomly divided into model group,fluorouracil group(5-FU group),modified Buzhong Yiqi formula group,Klotho group,and modified Buzhong Yiqi formula+Klotho group.The treatments administered included normal saline,5-FU(25 mg/kg),modified Buzhong Yiqi formula(53.43 g/kg),exogenous Klotho(0.01 mg/kg),and a combination of modified Buzhong Yiqi formula and exogenous Klotho.Continuous intervention lasted for 12 days.Tumor volume was measured on day 0,day 4,day 8 and day 12.The tumor mass was measured on the 12th day,and tissue pathology through was observed by HE staining.The expression levels of Klotho,Caspase-1,IL-1β,and IL-18 in tumor tissue were assessed using immunohistochemistry.Results:Compared to the model group,the tumor masses of nude mice decreased significantly in the 5-FU group,modified Buzhong Yiqi formula group,Klotho group,and modified Buzhong Yiqi formula+Klotho group(P＜0.01 or P＜0.05).On the 4th,8th and 12th days post-treatment,the 5-FU group,modified Buzhong Yiqi formula group,Klotho group,and modified Buzhong Yiqi formula+Klotho group showed lower tumor volumes than model group(P＜0.01).The increase in transplanted tumor volume after treatment was lower in all treatment groups than in the model group.HE staining showed that in the post-treatment sections,there was nuclear shrinkage,cytoplasmic vacuolation,loose cell arrangement,and increased collagen fibers in the interstitium.Immunohistochemical results demonstrated that the 5-FU group,modified Buzhong Yiqi formula group,Klotho group,and modified Buzhong Yiqi formula+Klotho group showed higher expression of Klotho than model group(P＜0.01 or P＜0.05),and that the modified Buzhong Yiqi formula group,Klotho group,and modified Buzhong Yiqi formula+Klotho group showed lower expressions of Caspase-1,IL-1β and IL-18 than model group(P＜0.01 or P＜0.05).Conclusion:The modified Buzhong Yiqi formula can effectively inhibit the growth of colorectal cancer xenografts in nude mice.Its mechanism may be related to the up-regulation of Klotho expression,inhibition of Caspase-1-dependent pyroptosis,and reduction in the release of pro-inflammatory factors(IL-1β and IL-18).关键词
结直肠癌/补中益气加味方/Klotho/细胞焦亡/胱天蛋白酶-1/白细胞介素-1β/白细胞介素-18/裸鼠Key words
colorectal cancer/modified Buzhong Yiqi formula/Klotho/pyroptosis of cells/Caspase-1/IL-1β/IL-18/nude mice分类
医药卫生引用本文复制引用
王伟,周望潮,谢彪..补中益气加味方对裸鼠结直肠癌移植瘤Klotho蛋白及Caspase-1、IL-1β、IL-18表达的影响[J].中医药导报,2025,31(12):14-19,6.基金项目
国家自然科学基金项目(82374545) （82374545）
袁长津全国名中医传承工作室建设项目 （）
