枸杞多糖通过促进胆囊癌细胞铁死亡抑制其恶性进展  

Lycium Barbarum Polysaccharide Inhibits the Malignant Progression of Gallbladder Cancer Cells by Promoting Cellular Ferroptosis

作　　者：辛国军[1] 王建承[2] 杨勇[1] 雷鹏[3] 张亚文 李宝定[1] 张多强[1] 梁琦 卜阳 Xin Guojun;Wang Jiancheng;Yang Yong(Department of Hepatobiliary Surgery,People's Hospital of Ningxia Hui Autonomous Region(Ningxia Medical University Affiliated People's Hospital of Autonomous Region),Yinchuan 750002,China;Department of Pancreatic Surgery Centre,Ruijin Hospital Affiliated to Shanghai Jiaotong University Medical College,Shanghai 200025,China)

机构地区：[1]宁夏回族自治区人民医院(宁夏医科大学附属自治区人民医院)肝胆外科,银川750002 [2]上海交通大学医学院附属瑞金医院胰腺外科中心,上海200025 [3]宁夏医科大学总医院肝胆外科,银川750003

出　　处：《华中科技大学学报（医学版）》2024年第4期452-457,共6页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：宁夏回族自治区自然科学基金资助项目(No.2023AAC03506)。

摘　　要：目的探究枸杞多糖(LBP)通过调控细胞铁死亡对胆囊癌细胞(NOZ和SGC-996)增殖和转移的影响。方法不同剂量的LBP处理体外培养NOZ和SGC-996细胞;将细胞分为对照组(Control)、20μmol/LLBP组、40μmol/LLBP组、60μmol/LLBP组、80μmol/LLBP组、LBP+Fer-1组。用MTT法检测细胞活力;EdU法检测细胞增殖能力;Tran swell检测细胞侵袭能力;比色法检测Fe^(2+)的水平,BODIPYTM581/591C11分子探针测定活性氧(ROS)和丙二醛(MDA)的水平;Westernblot检测铁死亡相关蛋白谷胱甘肽过氧化物酶4(GPX4)酰基辅酶a合成酶长链家族成员4(ACSL4)、β-catenin和Wnt3A蛋白表达。结果与对照组比较,40μmol/LLBP组、60μmol/LLBP组细胞活力、增殖、侵袭能力显著降低(均P<0.05),Fe^(2+)水平、ROS、MDA活性明显增加(均P<0.05),GPX4、β-catenin和Wnt3A蛋白表达显著减少,ACSL4蛋白表达明显增加(均P<0.05)。与LBP组比较,LBP+Fer-1组细胞活力、增殖、侵袭能力显著提高(均P<0.05)。结论LBP通过诱导胆囊癌细胞铁死亡进而抑制其细胞的增殖和转移。Objective To investigate the effects of lycium barbarum polysaccharide(LBP)on the proliferation and metastasis of gallbladder cancer cells(NOZ and SGC-996)by regulating cellular ferroptosis.Methods NOZ and SGC-996 cells were cultured in vitro by treatment with different doses of LBP.The cells were divided into control group,20μmol/L LBP group,40μmol/L LBP group,60μmol/L LBP group,80μmol/L LBP group,and LBP+Fe-1 groups.Cell activity was detected by MTT assay.Cell proliferation was detected by EdU assay.Cell invasion ability was detected by Transwell assay.Fe^(2+)level was detected by colorimetric assay,reactive oxygen species(ROS)and malondialdehyde(MDA)levels were determined by BODIPY~(TM)581/591 C11 molecular probe.Western blot was used to detect glutathione peroxidase 4(GPX4),acyl-CoA Synthetase long-chain family member 4(ACSL4),β-catenin,and Wnt3A protein expression.Results Compared with the control group,cell viability,proliferation,and invasion were significantly decreased in the 40μmol/L LBP,and 60μmol/L LBP groups(all P<0.05),and Fe^(2+)level,ROS,and MDA activities were significantly increased(all P<0.05),and GPX4,β-catenin,and Wnt3A protein expressions were significantly reduced,and ACSL4 protein expression was significantly increased(all P<0.05).Compared with the LBP group,cell viability,proliferation,and invasion ability were significantly increased in the LBP+Fer-1 group(all P<0.05).Conclusion LBP inhibits the proliferation and metastasis of gallbladder cancer cells by inducing ferroptosis.

关 键 词：枸杞多糖 铁死亡 胆囊癌 增殖 侵袭 谷胱甘肽过氧化物酶4 

分 类 号：R735.8[医药卫生—肿瘤]