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
郭建辉 1李晓辉 1王辰啸 1陈华涛 1吴彪 1瞿紫微1
作者信息
- 1. 武汉市第一医院胃肠外科,湖北 武汉 430022
- 折叠
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+10 μmol/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.
Abstract
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 resec-ted 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+10 μmol/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.Observa-tion 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 de-creased(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Key words
Celastrus orbiculatus extracts/Colon cancer/Tumor-infiltrating lymphocyte/Ferroptosis/Glutathione引用本文复制引用
基金项目
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)
出版年
2024
NETL
NSTL
万方数据