摘要
目的研究9-甲基哌嗪甲基-10-羟基喜树碱氮氧化物(HCNO-YCS-03)对肺癌A549细胞体内、外抑制作用及乏氧选择性。方法采用MTT法和流式细胞术检测HCNO-YCS-03在常氧和乏氧环境下对A549细胞的体外抑制作用。24只裸鼠建立肺癌A549移植瘤模型,均分为三组,分别给予生理盐水、HCNO-YCS-03 5 mg/kg和HCNO-YCS-03 10mg/kg。观察肿瘤体积变化,TUNEL法检测肿瘤组织的细胞凋亡率。结果 HCNO-YCS-03在常氧环境下对A549细胞的IC50值高于乏氧环境[(16.1±1.6)μg/ml vs.(3.3±0.5)μg/ml](P<0.05)。常氧和乏氧环境下HCNOYCS-03呈时间、剂量依赖性增加A549细胞凋亡率(P<0.05),乏氧环境下增加幅度更为显著(P<0.05)。与生理盐水组相比,HCNO-YCS-03 5mg/kg和10mg/kg均能增加肿瘤组织的细胞凋亡率(P<0.05)、抑制肿瘤生长(P<0.05),其肿瘤抑制率分别为31.4%和49.7%。结论 HCNOYCS-03具有很好的乏氧选择性,在体内、外均能有效抑制肺癌A549细胞生长。
Objective To investigate the inhibitory effect and hypoxia selectivity of HCNO- YCS-03 on lung cancer A549 cells in vitro and in vivo. Methods The inhibitory effect of HCNO-YCS- 03 on A549 cells exposed to normal oxygen and hypoxia in vitro was detected by MTT assay and flow cytometry. A total of 24 nude mice was injected with A549 cells to establish xenograft model and then equally randomized into three groups of normal saline, HCNO-YCS-03 5 mg/kg and HCNO-YCS-03 10 mg/kg. The change of tumor volume was observed, and the cell apoptosis in the tumor tissues was determined by TUNEL assay. Results The IC50 value of HCNO-YCS-03 for A549 cells exposed to normal oxygen was higher than that exposed to hypoxia[（16.1±1. 6） μg/ml vs. （3. 3±0. 5）μg/ml] （P〈0. 05）. HCNO-YCS-03 enhanced the apoptosis of A549 cells exposed to normal oxygen and hypoxia in the time- and dose-dependent manners（P〈0. 05）, which was more obvious under hypoxia microenvironment（P〈0. 05）. Compared with normal saline group, HCNO-YCS-03 5 mg/kg and 10 mg/kg could promote cell apoptosis in the tumor tissues and inhibit tumor growth with the inhibition rates of 31.4% and 49. 7% ,respectively（P〈0. 05）. Conclusion HCNO-YCS-03 with good hypoxia selectivity can effectively inhibit the growth of A549 cells in vivo and in vitro.
出处
《江苏医药》
CAS
北大核心
2014年第3期261-264,共4页
Jiangsu Medical Journal
基金
国家自然科学基金青年基金(81102317)
江苏省自然科学基金(BK2007004)
关键词
肺癌
喜树碱
乏氧微环境
Lung cancer
Camptothecin
Hypoxia microenvironment
