去铁铵在结肠癌细胞株的放疗增敏作用及机制研究  

Study on the Radiosensitization Effect and Mechanism of Deferoxamine in Colon Cancer Cell Lines

作　　者：陈宗艺 毛久昂 王振欣[1] CHEN Zong-yi;MAO Jiu-ang;WANG Zhen-xin(Department of Medical Oncology,First Affiliated Hospital of Soochow University,Suzhou,Jiangsu,215006,China)

机构地区：[1]苏州大学附属第一医院肿瘤科,江苏苏州215006

出　　处：《中国血液流变学杂志》2024年第1期27-31,76,共6页Chinese Journal of Hemorheology

基　　金：江苏省高等学校大学生创新创业训练项目(202210285071Z)。

摘　　要：目的探讨去铁铵(deferoxamine,DFO)对结肠癌细胞株SW480和HT29的放射增敏作用及机制。方法通过CCK-8法检测细胞增殖活力,评估不同浓度或剂量的DFO和电离辐射(ionizing radiation,IR)对人结肠癌细胞株SW480及HT29的杀伤效应;将细胞分为未处理对照组、DFO处理组、单独IR组,以及DFO和IR共处理组,Western blot检测各组细胞铁代谢相关蛋白DMT1、FPN1、FTH和FTL蛋白表达水平,上皮间质转化(epithelial-mesenchymal transition,EMT)相关蛋白SNAI1、Vimentin、E-cadherin表达水平。结果不同浓度或剂量的DFO或IR处理后,HT29和SW480细胞增殖活力均呈时间依赖和浓度/剂量依赖的方式降低,差异均具有统计学意义(P<0.05)。HT29细胞对DFO更敏感,而SW480细胞对IR更加敏感。免疫印迹结果显示,SW480细胞中DFO、IR或共处理后DMT1、FPN1、FTH和FTL的蛋白表达均增加。其中,IR处理组DMT1表达升高最显著,并且被DFO共处理逆转。HT29细胞中各处理组DMT1、FPN1蛋白表达变化与SW480细胞一致,但FTH、FTL蛋白表达降低。SW480细胞中,DFO或IR处理后SNAI1、Vimentin蛋白表达增加,E-cadherin表达降低;DFO共处理逆转这一趋势;HT29细胞中,各处理组SNAI1蛋白表达均降低,E-cadherin蛋白表达均增加。两个细胞IR处理后Vimentin蛋白表达均增加,并被DFO逆转。结论结肠癌细胞SW480和HT29对DFO和IR具有不同的敏感性,DFO可能通过增强铁代谢和抑制EMT增强结肠癌细胞的放射敏感性。Objective To explore the radiosensitizing effect and mechanism of deferoxamine(DFO)on colon cancer cell lines SW480 and HT29.Methods CCK-8 method was used to detect cell proliferation activity,and the killing effects of different concentrations or doses of DFO and ionizing radiation(IR)on human colon cancer cell lines SW480 and HT29 were evaluated.The cells were divided into untreated control group,DFO treated group,IR alone group,and DFO and IR co-treatment group.Western blot was used to detect the expression levels of iron metabolism-related proteins DMT1,FPN1,FTH and FTL,and epithelial-mesenchymal transition(EMT)-related proteins SNAI1,Vimentin and E-cadherin in each group.Results After treatment with different concentrations of DFO or doses of IR,the cell viability of HT29 and SW480 cells reduced in a time-and concentration/dose-dependent manner with a statistically significantly difference(P<0.05).HT29 cells are more sensitive to DFO,while SW480 cells are more sensitive to IR.Western blot results showed that compared with control group,protein expression of DMT1,FPN1,FTH and FTL in SW480 cells increased after DFO,IR or co-treatment.Among them,the expression of DMT1 increased most significantly in the IR treatment group,and was reversed by co-treatment with DFO.The changes in DMT1 and FPN1 protein expression in each treatment group in HT29 cells were consistent with those in SW480 cells,but the expression of FTH and FTL proteins decreased.In SW480 cells,SNAI1 and Vimentin protein expression increased,and E-cadherin expression decreased after DFO or IR treatment.DFO co-treatment reversed this trend.In HT29 cells,SNAI1 protein expression decreased and E-cadherin protein expression increased in each treatment group.Vimentin protein expression increased in both cells after IR treatment and was reversed by DFO.Conclusion Colon cancer cells SW480 and HT29 have different sensitivities to DFO and IR,and DFO may enhance the radiosensitivity of colon cancer cells by enhancing iron metabolism and inhibiting EMT.

关 键 词：去铁铵 结肠癌 放疗增敏 铁代谢 EMT 

分 类 号：R735.35[医药卫生—肿瘤] R730.55[医药卫生—临床医学]