HIF-1α/2α介导塞来昔布在不同给氧条件下对A549细胞的抑制作用  

HIF-1α/2α mediates the inhibitory effect of celecoxib on lung adenocarcinoma A549 cells under different oxygen conditions

作　　者：周超 王昱升 施晓倩 尹基忠 李兵[1] ZHOU Chao;WANG Yu-sheng;SHI Xiao-qian;YIN Ji-zhong;LI Bing(Department of Respiratory and Critical Care Medicine,Changzheng Hospital,Naval Medical University(Second Military Medical University),Shanghai 200003,China;Department of Respiratory and Critical Care Medicine,Shanghai Fourth People's Hospital,Tongji University,Shanghai 200439,China)

机构地区：[1]海军军医大学(第二军医大学)长征医院呼吸与危重症医学科,上海200003 [2]上海同济大学附属第四人民医院呼吸与危重症医学科,上海200439

出　　处：《军事医学》2022年第4期298-303,共6页Military Medical Sciences

基　　金：国家自然科学基金项目(82074065,81672929和81602618)。

摘　　要：目的 探讨在不同给氧条件下,塞来昔布对肺腺癌细胞的抑制作用及机制,为临床应用塞来昔布辅助治疗阻塞性睡眠呼吸暂停综合征(OSAS)、慢性阻塞性肺疾病(COPD)等缺氧性疾病合并肺癌提供理论依据。方法按照常氧(21%O_(2))、持续性低氧(1%O_(2))及间歇性低氧(1%O_(2)1 h+21%O_(2)0.5 h 交替)将 A549 细胞随机分为 3 组并分别给予塞来昔布干预,应用Western印迹测定低氧诱导因子(HIF)-1α、HIF-2α、环氧化酶2(COX-2)蛋白的表达水平,Transwell法检测细胞迁移和侵袭能力,CCK-8法检测细胞增殖活性。结果①与常氧组相比,两个低氧组HIF-1α/2α、COX-2的表达显著增加,其中间歇性低氧组更加显著;②与常氧组相比,两个低氧组 A549细胞的增殖、迁移及侵袭能力均提高,且间歇性低氧组更为显著;塞来昔布在3种给氧条件下均可对A549细胞的增殖、迁移及侵袭能力起到抑制作用。结论 间歇性低氧可诱导 HIF-1α/2α、COX-2 高表达,较慢性持续性低氧更为显著,而塞来昔布在不同给氧条件下均能抑制肺腺癌细胞的增殖活性、迁移和侵袭能力。Objective To investigate the inhibitory effect and mechanism of celecoxib on lung adenocarcinoma cells under different oxygen conditions,and to provide data for clinical application of celecoxib in the adjuvant treatment of such hypoxic diseases as obstructive sleep apnea syndrome(OSAS)and chronic obstructive pulmonary disease(COPD)combined with lung cancer. Methods A549 cells were randomly divided into three groups :the normoxia group(21% O_(2)),continuous hypoxia group(1%O_(2))and intermittent hypoxia group(1%O_(2)1 h+21%O_(2)0.5 h cycle)and treated with celecoxib,respectively. The expressions of hypoxia-inducible factor-1α(HIF)-1α,HIF-2α and cyclooxygenase-2(COX-2)proteins were detected by Western blotting,the migration and invasion ability was detected by Transwell assay,and the proliferation activity was detected by cell counting kit(CCK-8)assay. Results (1)Compared with the normoxia group,the expressions of HIF-1α/2α and COX-2 were significantly increased in the hypoxia group,especially in the intermittent hypoxia group. (2)Compared with the normoxic group,the proliferation,migration and invasion of A549cells were increased under hypoxic conditions,especially under intermittent hypoxic conditions. Celecoxib inhibited the proliferation,migration and invasion of A549 cells under the three oxygen conditions. Conclusion Intermittent hypoxia can induce significantly higher expressions of HIF-1α/2α and COX-2 than continuous hypoxia. Celecoxib can significantly inhibit the proliferation,migration and invasion of lung adenocarcinoma cells under different oxygen conditions.

关 键 词：低氧 低氧诱导因子 环氧化酶2 塞来昔布 肺腺癌 

分 类 号：R734.2[医药卫生—肿瘤]