ALKBH3在肺腺癌中的表达及对肺腺癌A549细胞增殖、迁移和侵袭的影响  

Expression of ALKBH3 in lung adenocarcinoma and its effect on proliferation,migration and invasion of lung adenocarcinoma A549 cells

作　　者：陈浩宇 秦超 颜航 刘涛[1] 张松[1] 唐晟杰 周海宁 CHEN Haoyu;QIN Chao;YAN Hang;LIU Tao;ZHANG Song;TANG Shengjie;ZHOU Haining(Department of Thoracic Surgery,Suining Central Hospital Affiliated to Chongqing Medical University,Sichuan Suining 629000,China;Basic Laboratory,Suining Central Hospital Affiliated to Chongqing Medical University,Sichuan Suining 629000,China)

机构地区：[1]重庆医科大学附属遂宁市中心医院胸外科,四川遂宁629000 [2]重庆医科大学附属遂宁市中心医院基础实验室,四川遂宁629000

出　　处：《现代肿瘤医学》2025年第6期893-901,共9页Journal of Modern Oncology

基　　金：四川省卫生健康委员会医学科技项目(编号:21PJ188)。

摘　　要：目的:探索α-酮戊二酸依赖性双加氧酶同源物3(alpha-ketoglutarate-dependent dioxygenase homolog 3,ALKBH3)在肺腺癌组织中的表达及其对肺腺癌A549细胞增殖、迁移和侵袭的影响,以其为肺腺癌的诊疗提供新思路。方法:采用组织微阵列芯片(tissue microarrays,TMAs)进行免疫组织化学(immunohistochemistry,IHC)染色,检测ALKBH3在癌组织和癌旁组织中的表达水平;收集12对新鲜肺腺癌及配对癌旁组织标本提取蛋白,Western blot检测蛋白水平表达情况;收集4对新鲜肺腺癌及配对癌旁组织提取RNA,RT-qPCR检测ALKBH3 mRNA水平表达情况;利用慢病毒干扰RNA技术敲低ALKBH3表达;再通过RT-qPCR和Western blot检测ALKBH3敲低效率;CCK-8、细胞划痕实验及Transwell侵袭实验分别检测敲低ALKBH3对肺腺癌A549细胞增殖、迁移和侵袭的影响;裸鼠皮下成瘤实验检测敲低ALKBH3对人肺腺癌A549细胞成瘤能力的影响。结果:与癌旁组织相比,ALKBH3在肺腺癌组织中表达明显上调,蛋白质和mRNA表达水平也显著提高(P<0.05);敲低ALKBH3后肺腺癌A549细胞增殖、迁移和侵袭能力均受到明显抑制(P<0.05);敲低ALKBH3后,裸鼠皮下肿瘤体积、重量明显降低。结论:ALKBH3在肺腺癌组织中高表达,在体内及体外实验中敲低ALKBH3可抑制肺腺癌A549细胞增殖、迁移和侵袭及皮下成瘤能力。Objective:To explore the alpha ketoglutarate-dependent dioxygenase homolog 3(ALKBH3)expression in lung adenocarcinoma tissue and its effect on proliferation,migration and invasion of lung adenocarcinoma A549 cells,to provide a new way for diagnosis and treatment of lung adenocarcinoma.Methods:Immunohistochemistry(IHC)was conducted using tissue microarrays(TMAs)to detect the expression level of ALKBH3 in cancer tissue and adjacent tissue.Protein was extracted from 12 pairs of fresh lung adenocarcinoma and paired adjacent tissue samples,and protein expression was detected by Western blot.Collect 4 pairs of fresh lung adenocarcinoma tissue and corresponding adjacent tissue to extract RNA,then RT-qPCR was used to detect the expression level of ALKBH3 mRNA.ALKBH3 expression was knocked down by lentivirus interfering RNA technique.The knock-down efficiency of ALKBH3 was detected by RT-qPCR and Western blot.The effects of knockdown ALKBH3 on the proliferation,migration and invasion of lung adenocarcinoma A549 cells were detected by CCK-8,cell scratch assay and Transwell invasion assay,respectively.The effect of knockdown ALKBH3 on tumorigenic ability of human lung adenocarcinoma A549 cells was detected by subcutaneous tumorigenic experiment in nude mice.Results:Compared with adjacent tissue,ALKBH3 expression in lung adenocarcinoma tissue was significantly up-regulated,and the expression levels of ALKBH3 protein and mRNA were also significantly increased(P<0.05).After ALKBH3 knockdown,the proliferation,migration and invasion ability of lung adenocarcinoma A549 cells were significantly inhibited(P<0.05).After ALKBH3 was knocked down,the subcutaneous tumor volume and weight of nude mice were significantly reduced.Conclusion:ALKBH3 is highly expressed in lung adenocarcinoma tissue,and knocking down ALKBH3 can inhibit the proliferation,migration,invasion and subcutaneous tumorigenesis of lung adenocarcinoma A549 cells in vivo and in vitro.

关 键 词：肺腺癌 ALKBH3 细胞增殖 细胞迁移 细胞侵袭 

分 类 号：R734.2[医药卫生—肿瘤]