右美托咪定对低氧诱导肺癌细胞转移能力的影响

The effects of dexmedetomidine on hypoxia-induced metastasis of lung cancer cells

目的观察右美托咪定对低氧诱导人肺腺癌细胞A549转移能力的影响及相关机制。方法人肺腺癌细胞A549接种于培养板,培养24 h后,采用随机数字表法,将其随机分为4组:对照组(C组)、低氧组(H组)、低氧组+右美托咪定组(HD组)、低氧+右美托咪定+阿替美唑组(HDA组)。C组为正常培养组,H组采用94%N_2—5%CO_2—1%O_2处理4 h,HD组采用94%N2—5%CO_2—1%O_2和1 nmol/L右美托咪定处理4 h。HDA组采用94%N_2—5%CO_2—1%O_2、1 nmol/L右美托咪定和10 nmol/L阿替美唑处理4 h。采用Transwell法检测细胞侵袭能力,细胞划痕法检测细胞迁移能力;采用免疫荧光实验检测低氧诱导因子-1α(HIF-1α)、波形蛋白(Vimentin)、纤连蛋白(Fibronectin)表达。结果与C组比较,H组细胞侵袭能力和迁移能力增加,HIF-1α、Vimentin、Fibronectin蛋白表达上调(P <0. 05);与H组比较,HD组细胞侵袭能力和迁移能力增加,HIF-1α、Vimentin、Fibronectin蛋白表达上调(P <0. 05);与HD组比较,HDA组细胞侵袭能力和迁移能力降低,HIF-1α、Vimentin、Fibronectin蛋白表达下调(P <0. 05)。结论右美托咪定可促进低氧诱导人肺腺癌细胞A549的转移能力,其机制可能与激动α_2肾上腺素能受体、上调HIF-1α/上皮间质转化通路活性有关。

Objective To investigate the effects of dexmedetomidine on hypoxia-induced metastasis of lung cancer cells. Methods Human lung adenocarcinoma A549 cells were inoculated. After being cultured for 24 h,the cells were randomly divided into 4 groups,Group Control( C),Group Hypoxia( H),Group Hypoxia + dexmedetomidine( HD),and Group Hypoxia + dexmedetomidine + Atipamezole( HDA). The cells of Group C were exposed to 95% air-5% CO2 for 4 h. The cells of Group H were exposed to 94% N2-5% CO2-1% O2 for 4 h. The cells of Group HD were exposed to 94% N2-5% CO2-1% O2 and treated with 1 nmol/L dexmedetomidine for 4 h. The cells of Group HDA were exposed to 94% N2-5% CO2-1% O2 and treated with 1 nmol/L dexmedetomidine and 10 nmol/L Atipamezole for 4 h.The invasive ability of cells was determined by trans-well assay. The migration capacity was evaluated by wound healing assay. The expression of HIF-1α,vimentin,and fibronectin proteins were assessed by Western blot. Results Compared with Group C,the invasive and migration capacities of cells in Group H were significantly increased,and the protein expression of HIF-1α,vimentin,and fibronectin proteins was significantly up-regulated( P < 0. 05). Compared with Group H,the invasive and migration capacities of cells in Group HD were significantly increased,and the protein expression of HIF-1α,vimentin,and fibronectin was significantly up-regulated( P < 0. 05). Compared with Group HD,the invasive and migration capacities of cells in Group HDA were significantly decreased,and the protein expression of HIF-1α,vimentin,and fibronectin was significantly down-regulated( P < 0. 05). Conclusion Dexmedetomidine inhibits the hypoxia-induced metastasis of lung cancer cells,which might be through activating α2 adrenergic receptor and up-regulating the epithelial-mesenchymal transition pathway.