文章摘要
陈小红,黄 涛,门艳华,吴溧兴,曹汉忠.氯胺酮对人肺癌A549细胞生长的影响及相关机制研究[J].南京医科大学学报,2015,(10):1387~1392
氯胺酮对人肺癌A549细胞生长的影响及相关机制研究
The effect and mechanism of ketamine on proliferation of human lung adenocarcinoma A549 cells
投稿时间:2015-07-19  
DOI:10.7655/NYDXBNS20151011
中文关键词: A549细胞  氯胺酮  吗啡  NF-κB
英文关键词: A549  ketamine  morphine  NF-κB
基金项目:南通市市级科技计划(指导性,HS13928)
作者单位
陈小红 南通大学附属肿瘤医院麻醉科,江苏 南通 226361 
黄 涛 南通大学附属肿瘤医院麻醉科,江苏 南通 226361 
门艳华 南通大学附属肿瘤医院麻醉科,江苏 南通 226361 
吴溧兴 南京医科大学公共卫生学院,江苏 南京 210029 
曹汉忠 南通大学附属肿瘤医院麻醉科,江苏 南通 226361 
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中文摘要:
      目的:探讨麻醉类药物氯胺酮和吗啡对人肺癌A549细胞生长的影响及相关作用机制。方法:体外培养肺癌细胞系A549,细胞培养24 h后,随机分为3组:对照组(NC组,加0.9% NaCl处理)?氯胺酮组(K1?K2?K3组,分别加氯胺酮100?200?400 ?滋g/mL处理)和吗啡组(M1?M2?M3组,分别加吗啡25?50?100 ?滋g/mL处理)。持续作用24 h后,Transwell小室培养体系测定肿瘤细胞的迁移率;双荧光素酶报告基因法测定NF-κB转录活性;48 h后MTT法测定细胞增殖抑制率;Western blot技术测定NF-κB P65的蛋白表达;QPCR技术检测细胞内IL-1β和COX-2的mRNA表达。结果:①与NC组比较,M1?M2组表现为促进A549细胞迁移(P < 0.05),M3组作用不明显;K1?K2?K3组表现为抑制A549细胞迁移(P < 0.05);②与NC组比较,M1?M2组表现为促进A549细胞增殖(P < 0.05),M3组作用不明显;K2?K3组表现为抑制A549细胞增殖(P < 0.05),K1组不明显;③与NC组比较,M1?M2?M3组表现为促进IL-1β?COX-2的mRNA表达(P < 0.05);K2?K3组表现为抑制IL-1β?COX-2的mRNA表达(P < 0.05),K1组不明显;④与NC组比较,M1?M2?M3组表现为促进P65的转录和蛋白表达(P < 0.05),K1?K2?K3组表现为抑制P65的转录和蛋白表达(P < 0.05)。结论:与阿片类药物不同,氯胺酮通过NF-κB信号通路及其下游因子IL-1β和COX-2抑制人肺腺癌细胞A549的迁移和增殖,可能更适用于肺癌患者的术后镇痛。
英文摘要:
      Objective:To investigate the effect and mechanism of anesthetic ketamine and morphine on the proliferation of cultured human lung adenocarcinoma A549 cell. Methods:Human lung adenocarcinoma A549 cells were treated with different concentration of ketamine(K1,K2,K3 is 100,200,and 400 μg/mL,respectively)and morphine(M1,M2,M3 is 25,50 and 100 μg/mL,respectively)for 24 and 48 h. After cultured for 24 h,the effect of ketamine and morphine on the invasive ability of A549 cells were measured by transwell invasion. NF-κB transcription activity were determined by luciferase assay. After cultured for 48 h,the proliferation inhibition rates of A549 cells were assessed by methyl thiazolyl tetrazolium (MTT) assay. Protein expressions of NF-κB P65 were determined by Western blot. IL-1β and COX-2 expression were determined by QPCR. Results:(1)Compared with the control group,M1 and M2 enhanced A549 cell proliferation and migration (P < 0.05),while K1,K2 and K3 suppressed A549 cells migration(P < 0.05). (2)M1,M2 and M3 enhanced IL-1β and COX-2 expression(P < 0.05),but K2 and K3 had opposing effects(P < 0.05). M1,M2,and M3 enhanced NF-κB and P65 transcription activity and protein expressions(P < 0.05),while K1,K2 and K3 had opposing effects(P < 0.05). Conclusion:Unlike opioids,ketamine inhibits the proliferation and migration of A549 through NF-κB and its down stream factor IL-1β and COX-2,may be more suitable for lung cancer patients postoperative analgesia.
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