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%Na Cl处理)、氯胺酮组(K1、K2、K3组,分别加氯胺酮100、200、400μg/m L处理)和吗啡组(M1、M2、M3组,分别加吗啡25、50、100μg/m L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m RNA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m RNA表达(P<0.05);K2、K3组表现为抑制IL-1β、COX-2的m RNA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。
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 / m L,respectively)and morphine(M1,M2,M3 is 25,50 and 100 μg / m L,respectively)for24 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.
出处
《南京医科大学学报(自然科学版)》
CAS
CSCD
北大核心
2015年第10期1387-1392,共6页
Journal of Nanjing Medical University(Natural Sciences)
基金
南通市市级科技计划(指导性
HS13928)