阿霉素联合5-氟尿嘧啶通过Akt/mTOR通路治疗肺腺癌的研究  

Doxorubicin combined with 5-fluorouracil exerts anticancer effects via Akt/mTOR pathway on lung adenocarcinoma cancer

作　　者：刘东利[1] 胡海峰[1] 贺小龙[1] 胡丽娜[2] 

机构地区：[1]延安大学附属医院呼吸内科,716000 [2]宝鸡市中医医院呼吸科,721001

出　　处：《国际呼吸杂志》2017年第4期253-257,共5页International Journal of Respiration

摘　　要：目的 探讨阿霉素与5-氟尿嘧啶治疗肺腺癌的作用机制.方法 用MTT比色法与流式细胞术法检测32例肺腺癌患者肿瘤组织提取的细胞给药阿霉素和/或5-氟尿嘧啶后细胞凋亡情况.用Western blot法检测CoCl2诱导低氧情况下血管内皮生长因子（VEGF）、缺氧诱导因子1α（HIF-1α）、磷酸化蛋白激酶B（p-Akt）与磷酸化哺乳动物类雷帕霉素靶蛋白（p-mTOR）的表达水平.用Transwell法检测药物对细胞迁移与侵袭能力的影响.结果 给药72 h后,5-氟尿嘧啶组与阿霉素组细胞显著凋亡（P值均〈0.05）;联合组与对照组相比差异有显著统计学意义（P〈0.01）.药物处理细胞48 h后,各给药组VEGF、HIF-1α、p-Akt与p-mTOR蛋白的表达水平显著降低,其中联合组蛋白下降水平最为显著.给药48 h后,5-氟尿嘧啶与阿霉素可显著抑制细胞迁移与侵袭（P值均〈0.05）;联合组细胞迁移率与对照组相比差异有显著统计学意义（P〈0.01）.结论 阿霉素联合5-氟尿嘧啶可能是通过抑制Akt/mTOR信号通路对肺腺癌起到治疗的作用.Objective To investigate the mechanism of doxorubicin combined with 5-fluorouracil for the treatment of lung adenocarcinoma cancer.Methods Flow cytometric and MTT assay were used to detect apoptosis of cells extracted from tumor tissues of 32 lung adenocarcinoma cancer patients after doxorubicin,5-fluorouracil and combined treatment.The expressions of vascular endothelial growth factor （VEGF）,hypoxia-inducible factor-1α（HIF-1α）,phosphorylation of protein Kinase B （p-Akt） and phosphorylation of mammalian target of rapamycin （p-mTOR） were examined by Western blot during cobalt chloride-induced hypoxia.Transwell method was used to detect the effects of drugs on cell migration and invasion ability.Results After 200 mg/L 5-fluorouracil and 1 mg/L doxorubicin treatment for 72 hours,cell apoptosis significantly increased （all P 〈0.05）,there was significant difference in cell apoptosis between combined drug group and control group （P 〈0.01）.After drug treatment for 48 hours,the expressions of VEGF,HIF-1α,p-Akt and p-mTOR proteins were significantly decreased in each treated group,especially in combined drug group.After 5-fluorouracil or doxorubicin treatment for 48 hours,the migration and invasion of cell were significantly inhibited（all P 〈0.05）,there was significant difference in cell migration rate between combined drug group and control group（P 〈 0.01）. Conclusions Doxorubicin combined with 5-fluorouracil may exert anticancer effects on lung adenocarcinoma cancer via Akt/mTOR pathway.

关 键 词：肺癌 阿霉素 5-氟尿嘧啶 AKT/MTOR 血管内皮生长因子 缺氧诱导因子1Α 

分 类 号：R734.2[医药卫生—肿瘤]