南蛇藤提取物对结肠癌肿瘤浸润淋巴细胞抗肿瘤效果的影响及机制  

Effects and mechanism of Celastrus orbiculatus extracts on anti-tumor effect of tumor-infiltrating lymphocyte in colon cancer

作　　者：郭建辉 李晓辉[1] 王辰啸 陈华涛[1] 吴彪[1] 瞿紫微[1] GUO Jianhui;LI Xiaohui;WANG Chenxiao;CHEN Huatao;WU Biao;QU Ziwei(Department of Gastrointestinal Surgery,the First Hospital of Wuhan,Wuhan 430022,China)

机构地区：[1]武汉市第一医院胃肠外科,湖北武汉430022

出　　处：《胃肠病学和肝病学杂志》2024年第10期1329-1334,共6页Chinese Journal of Gastroenterology and Hepatology

基　　金：武汉市卫健委医学科研项目(WX21A11);武汉市卫健委医学科研项目(WX23Z23)。

摘　　要：目的探究南蛇藤提取物(Celastrus orbiculatus extracts,COE)对结肠癌肿瘤浸润淋巴细胞(tumor-infiltrating lymphocyte,TIL)抗肿瘤效果的影响及其机制。方法收集2022年4月至2022年7月经手术切除的22例结肠癌样本,分离提取TIL,经鉴定后进行体外培养。TIL分为对照组(正常培养)、COE组(40 mg/L COE)、COE+Erastin组(40 mg/L COE+10μmol/L Erastin),通过MTT、流式细胞术、生化检测各组TIL体外存活、杀伤能力、凋亡情况、氧化应激水平,Western blotting检测铁死亡相关蛋白表达,裸鼠体内异种移植实验观察抑瘤效果。结果与对照组相比,COE组、COE+Erastin组体外存活、杀伤能力、GSH、GPX4提高(P<0.05),凋亡水平、ROS、MDA、DMT1、TFR1下降(P<0.05);与COE组相比,COE+Erastin组体外存活、杀伤能力、GSH、GPX4下降(P<0.05),凋亡水平、ROS、MDA、DMT1、TFR1上升(P<0.05)。体内异种移植实验结果显示,与SW480、HCT-116空白组相比,对照组、COE组、COE+Erastin组肿瘤体积、重量减小(P<0.05);与对照组相比,COE组、COE+Erastin组肿瘤体积、重量进一步减小(P<0.05);与COE组相比,COE+Erastin组肿瘤体积、重量增大(P<0.05)。结论COE通过增强GSH信号通路抑制TIL铁死亡,延长TIL体外增殖能力,增强对结肠癌细胞的杀伤效果。Objective To explore the effects and mechanism of Celastrus orbiculatus extracts(COE)on the anti-tumor effect of tumor-infiltrating lymphocyte(TIL)in colon cancer.Methods Twenty two cases of colon cancer resected from Apr.to Jul.2022 were collected.TIL was isolated and cultured in vitro after identification.TIL was divided into control group(normal culture),COE group(40 mg/L COE)and COE+Erastin group(40 mg/L COE+10μmol/L Erastin).The in vitro survival,killing ability,apoptosis and oxidative stress of TIL in each group were detected by MTT,flow cytometry and biochemistry.Detection of ferroptosis related protein expression by Western blotting.Observation on the effect of tumor inhibition by xenotransplantation in vivo of nude mouse.Results Compared with the control group,the in vitro survival,killing ability,GSH and GPX4 of COE group and COE+Erastin group increased(P<0.05),while the level of apoptosis,ROS,MDA,DMT1 and TFR1 decreased(P<0.05).Compared with COE group,in vitro survival,killing ability,GSH and GPX4 decreased(P<0.05),while apoptosis level,ROS,MDA,DMT1 and TFR1 increased in COE+Erastin group(P<0.05).The results of xenotransplantation in vivo showed that compared with SW480 and HCT-116 blank group,the tumor volume and mass of control group,COE group and COE+Erastin group decreased(P<0.05).Compared with the control group,the tumor volume and mass of COE group and COE+Erastin group were further reduced(P<0.05).Compared with COE group,the volume and mass of tumor in COE+Erastin group increased(P<0.05).Conclusion COE inhibits TIL ferroptosis by enhancing GSH signal pathway,prolongs the proliferation ability of TIL in vitro,and enhances the killing effect on colon cancer cells.

关 键 词：南蛇藤提取物 结肠癌 肿瘤浸润淋巴细胞 铁死亡 谷胱甘肽 

分 类 号：R735.3[医药卫生—肿瘤]