华蟾素对肺癌NCI-A549移植瘤裸鼠的抑制作用及机制研究  

Inhibitory effect and mechanism of cinobufotalin on lung cancer NCI-A549 xenograft in nude mice

作　　者：熊飞 施嫣嫣[2] 沈久成[1] 程洪兰[1] 杭永付[3] XIONG Fei;SHI Yanyan;SHEN Jiucheng;CHENG Honglan;HANG Yongfu(The Second Affiliated Hospital of Soochow University,Suzhou 215000,Jiangsu,China;Suzhou Hospital of Traditional Chinese Medicine,Suzhou 215000,Jiangsu,China;The First Affiliated Hospital of Soochow University,Suzhou 215000,Jiangsu,China)

机构地区：[1]苏州大学附属第二医院 [2]苏州市中医医院 [3]苏州大学附属第一医院

出　　处：《中国临床药理学与治疗学》2018年第10期1103-1108,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金青年项目(81402830)

摘　　要：目的:研究华蟾素抗肺癌细胞NCI-A549的抗肿瘤活性及机制。方法:40只小鼠被随机分为4组:正常组、模型组、华蟾素组和顺铂组,检测各组小鼠的体质量变化、抑瘤率、血液和肝肾功能,应用Western blot分析凋亡相关蛋白表达情况。结果:华蟾素可显著抑制A549移植瘤的生长,对小鼠血液及肝肾功能无明显影响,各组抑瘤率分别为58. 0%和82. 3%,Western blot结果显示华蟾素可以显著上调Bax/Bcl-2的表达,促进cleaved-Casp3和cleaved-PARP的表达并抑制pAKT(ser473)的表达。结论:华蟾素可以显著抑制肺癌A549移植瘤的生长,其分子机制可能与抑制PI3K/AKT通路的活化,从而促进肿瘤细胞凋亡相关。AIM: To investigate the anti-tumor effect and mechanism of cinobufotalin on lung cancer cells NCI-A549. METHODS: Forty BALB/c nude mice were randomly divided into the normal group,the mock group,the cinobufotalin group and the DDP( cisplatin) group. Body weight change,tumor inhibition rate, blood function, liver and kidney function of the mice in each group were detected.Western blot was used to investigate the expression of apoptosis-associated proteins. RESULTS: Cinobufotalin significantly inhibited the growth of A549 xenograft,but had no significant effect on the blood,liver and kidney function of the mice. The tumor-inhibition rate of the cinobufotalin group and the DDP group was 58. 0% and 82. 3%,respectively. Western blot results showed that cinobufotalin significantly up-regulated the expression of Bax/Bcl-2,promoted the expression of cleaved-caspase-3,cleavedPARP, and inhibited the expression of p-AKT( ser473). CONCLUSION: Cinobufotalin can significantly inhibit the growth of lung cancer A549 xenograft. Its molecular mechanism might be related to the inhibition of PI3 K/AKT pathway activation.Based on this mechanism,cinobufotalin can accelerate cell apoptosis.

关 键 词：华蟾素 肺癌 移植瘤 凋亡 PI3K/AKT通路 

分 类 号：R965.2[医药卫生—药理学]