Loxl2对人结直肠癌细胞5-氟尿嘧啶耐药性及增殖能力的影响研究  

The effect of Loxl2 on 5-fluorouracil resistance and proliferation ability of human colorectal cancer cells

作　　者：邱志泽 邱诗琪 毛文利 林武 黄伟 彭祺祺 QIU Zhi-ze;QIU Shi-qi;MAO Wen-li(General Surgery Department,Zhuhai Integrated Traditional Chinese and Western Medicine Hospital,Zhuhai 519020,China)

机构地区：[1]珠海市中西医结合医院普通外科,519020 [2]珠海市中西医结合医院急诊科,519020 [3]珠海市中西医结合医院病理科,519020 [4]珠海市香洲区人民医院健康管理科,519020

出　　处：《中国现代药物应用》2025年第5期174-180,共7页Chinese Journal of Modern Drug Application

基　　金：珠海市科技计划医疗卫生项目(一般项目)(项目编号:ZH22036201210109PWC)。

摘　　要：目的探究赖氨酰氧化酶样蛋白2(Loxl2)对人结直肠癌细胞5-氟尿嘧啶(5-FU)耐药性及增殖能力的影响。方法生信分析结直肠癌、腺癌,癌组织、癌旁组织及不同病理分期中Loxl2的表达,免疫组化检测癌组织、癌旁组织内Loxl2的蛋白阳性表达率;分析不同结直肠癌组织内Loxl2的蛋白表达,选取典型细胞系,设置一系列5-FU浓度,确定各组细胞内Loxl2表达及细胞增殖活性;构建Loxl2过表达、沉默细胞系,确定不同组细胞迁移及凋亡能力。结果与癌旁组织对比,结直肠癌组织内Loxl2表达显著提升(P<0.05);随着结直肠癌病理分期提升,Loxl2表达提升(P<0.05);随着5-FU干预浓度提升,HCT116、SW48细胞内Loxl2表达逐渐提升,当5-FU干预浓度为20、40μM时,HCT116、SW48细胞内Loxl2表达最高(P<0.05);Loxl2表达在HCT116、SW48内得到成功过表达及沉默处理(P<0.05);随着5-FU干预浓度提升,HCT116、SW48细胞系的增殖活性逐渐降低(P<0.05);与Vector组对比,Loxl2组细胞增殖克隆能力提升,凋亡能力降低(P<0.05);与Scamble组对比,shLoxl2-1、shLoxl2-2两组细胞增殖克隆能力降低,凋亡能力提升(P<0.05)。结论Loxl2在结直肠癌组织内高表达,Loxl2过表达可以促进结直肠癌5-FU耐药细胞的增殖克隆能力,抑制细胞凋亡能力,促进肿瘤进展,值得临床进一步研究。Objective To Explore the effects of lysyl oxidase-like protein 2(Loxl2)on 5-fluorouracil(5-FU)resistance and proliferation ability in human colorectal cancer.Methods Bioinformatics analysis was performed on the expression of Loxl2 in colorectal cancer,adenocarcinoma,cancerous tissue,adjacent tissue,and different pathological stages.Immunohistochemistry was used to detect the positive expression rate of Loxl2 protein in cancerous tissue and adjacent tissue;analyze the expression of Loxl2 protein in different colorectal cancer tissues,select typical cell lines,set a series of 5-FU concentrations,and determine the expression of Loxl2 and cell proliferation activity in each group of cells;construct Loxl2 overexpressing and silencing cell lines to determine the migration and apoptosis abilities of different groups of cells.Results Compared with adjacent tissues,the expression of Loxl2 in colorectal cancer tissue was significantly increased(P<0.05);as the pathological upstaging of colorectal cancer increases,the expression of Loxl2 increased(P<0.05).As the intervention concentration of 5-FU increased,the expression of Loxl2 in HCT116 and SW48 cells gradually increased;when the intervention concentration of 5-FU was 20μM and 40μm,the expression of Loxl2 in HCT116 and SW48 cells was the highest(P<0.05).Loxl2 expression was successfully overexpressed and silenced in HCT116 and SW48(P<0.05);as the concentration of 5-FU intervention increased,the proliferation activity of HCT116 and SW48 cell lines gradually decreased(P<0.05).Compared with Vector group,Loxl2 group showed an increase in cell proliferation and cloning ability,while the apoptosis ability decreased(P<0.05).Compared with Scamble group,shLOXL2-1 and shLOXL2-2 groups showed a decrease in cell proliferation and cloning ability,and an increase in apoptosis ability(P<0.05).Conclusion Loxl2 is highly expressed in colorectal cancer tissue.Overexpression of Loxl2 can promote the proliferation and cloning ability of 5-FU resistant colorectal cancer cells,inhibit cell a

关 键 词：结直肠癌 赖氨酰氧化酶样蛋白2 肿瘤耐药 细胞活性 

分 类 号：R735.34[医药卫生—肿瘤]