双硫仑联合紫杉醇对食管癌细胞增殖、侵袭能力的抑制作用及其机制  

Inhibitory effects of disulfiram combined with paclitaxel on proliferation and invasion of esophageal cancer cells and their mechanism

作　　者：冯晓延 熊荣生[1] 许可[1] 徐谊 王浩 FENG Xiaoyan;XIONG Rongsheng;XU Ke;XU Yi;WANG Hao(Department of Thoracic Surgery,Nanxishan Hospital of Guangxi Zhuang Autonomous Region,Guilin 541002,China)

机构地区：[1]广西壮族自治区南溪山医院胸外科,广西桂林541002

出　　处：《山东医药》2024年第5期26-30,共5页Shandong Medical Journal

基　　金：广西壮族自治区卫生健康委员会自筹课题项目(Z20180553);广西医疗卫生重点培育学科建设项目[桂卫科教发(2023)1号]。

摘　　要：目的探讨双硫仑联合紫杉醇对食管癌细胞增殖、侵袭能力的抑制作用并分析其机制。方法以不同浓度双硫仑(0、10、20、40μmol/L)分别作用于食管癌细胞株TE-1和TE-10,CCK-8法测算细胞活力,筛选得到双硫仑最佳作用浓度为20μmol/L。将TE-1、TE-10食管癌细胞分别分为对照组(不加药物正常培养)、双硫仑组(20μmol/L双硫仑)、紫杉醇组(0.5μmol/L紫杉醇)、双硫仑+紫杉醇组(20μmol/L双硫仑+0.5μmol/L紫杉醇)。采用MTT法观察细胞增殖能力,流式细胞术观察细胞凋亡率,Transwell实验观察细胞侵袭能力,RT-qPCR法检测细胞α微管蛋白mRNA,Western blotting法检测细胞α微管蛋白、Bcl-2蛋白。结果TE-1及TE-10细胞增殖率对照组>双硫仑组>紫杉醇组>双硫仑+紫杉醇组,TE-1及TE-10细胞凋亡率对照组<双硫仑组<紫杉醇组<双硫仑+紫杉醇组(P均<0.05),TE-1及TE-10细胞穿膜细胞数对照组>双硫仑组>紫杉醇组>双硫仑+紫杉醇组(P均<0.05)。TE-1细胞α微管蛋白mRNA表达对照组>双硫仑组>紫杉醇组>双硫仑+紫杉醇组,TE-10细胞α微管蛋白mRNA表达对照组>双硫仑组>紫杉醇组、双硫仑+紫杉醇组;TE-1及TE-10细胞α微管蛋白、Bcl-2蛋白表达对照组>双硫仑组>紫杉醇组>双硫仑+紫杉醇组(P均<0.05)。结论双硫仑联合紫杉醇可增强对食管癌细胞增殖、侵袭能力的抑制作用,其机制可能与降低细胞中微管蛋白表达、促进细胞凋亡有关。Objective To investigate the inhibitory effects of disulfiram combined with paclitaxel on the proliferation and invasion of esophageal cancer cells and their mechanism.Methods The esophageal cancer cell lines TE-1 and TE-10 were treated with different concentrations of disulfiram(0,10,20,40μmol/L),and the cell viability was measured by CCK-8 method to screen the optimal concentration of disulfiram.The intervention concentration of disulfiram was 20μmol/L.TE-1 and TE-10 esophageal cancer cells were divided into the control group(normal culture without drugs),disulfiram group(20μmol/L disulfiram),paclitaxel group(0.5μmol/L paclitaxel),disulfiram+paclitaxel group(20μmol/L disulfiram+0.5μmol/L paclitaxel),respectively.MTT assay was used to observe the cell proliferation,flow cytometry was used to observe the apoptosis rate,Transwell assay was used to observe the cell invasion ability,RT-qPCR was used to detect the mRNA ofα-tubulin,and Western blotting was used to detect the protein expression levels ofα-tubulin and B-cell lymphoma-2(Bcl-2).Results The proliferation rates of TE-1 and TE-10 cells were in the following order:control group>disulfiram group>paclitaxel group>disulfiram+paclitaxel group,apoptosis rates of TE-1 and TE-10 cells were as follows:control group<disulfiram group<paclitaxel group<disulfiram+paclitaxel group,the number of transmembrane TE-1 and TE-10 cells was as follows:control group>disulfiram group>paclitaxel group>disulfiram+paclitaxel group,the expression of α-tubulin mRNA in TE-1 cells was as follows:control group>disulfiram group>paclitaxel group>disulfiram+paclitaxel group,the expression of α-tubulin mRNA in TE-10 cells was in the following order:control group>disulfiram group>paclitaxel group,disulfiram+paclitaxel group,and the expression levels of α-tubulin and Bcl-2 protein in TE-1 and TE-10 cells were as follows:control group>disulfiram group>paclitaxel group>disulfiram+paclitaxel group(all P<0.05).Conclusion Disulfiram combined with paclitaxel may enhance the inhibitory effec

关 键 词：双硫仑 食管癌 紫杉醇 微管蛋白 细胞增殖 细胞侵袭 

分 类 号：R735.1[医药卫生—肿瘤]