红海杆菌属海洋细菌产物Blue-Ⅰ对人胃腺癌细胞生长的影响  

Effects of Blue-Ⅰ,a metabolite from marine Rhodomarinobacter spp. on proliferation of human gastric cancer cells

作　　者：袁保红[1] 杨国武[2] 曹理想[3] 蔡创华[4] 林永成[5] 周世宁[3] 

机构地区：[1]广东药学院,广东广州510006 [2]深圳市计量质量检测研究院,广东深圳518055 [3]中山大学生命科学学院,广东广州510275 [4]中国科学院南海海洋研究所,广东广州510301 [5]中山大学化学化工学院,广东广州510275

出　　处：《中国药理学与毒理学杂志》2006年第6期473-478,共6页Chinese Journal of Pharmacology and Toxicology

基　　金：国家高技术研究发展计划(863)资助项目2003AA620401)~~

摘　　要：目的研究一种新的红海杆菌属(Rhodomari-nobacter)海洋细菌所产生的次级代谢产物Blue-Ⅰ是否抑制胃腺癌细胞生长。方法用MTT法测得Blue-Ⅰ对人胃腺癌细胞MCG803的IC50;单细胞凝胶电泳观察MCG803细胞是否发生DNA损伤;用Hoechest33258染色法和流式细胞仪检测MCG803细胞凋亡及细胞周期的改变。结果Blue-Ⅰ抑制MCG803细胞的生长,IC50为(4.6±1.1)mg·L-1;Blue-Ⅰ引起MCG803细胞基因组的降解,2.5,5和10mg·L-1Blue-Ⅰ处理后MCG803细胞彗星实验的拖尾率由对照组(4.2±1.2)%上升到(23.2±4.9)%,(51.4±6.9)%和(68.7±6.5)%,拖尾细胞的平均尾长随着处理浓度的升高而显著升高;用Hoechest33258染色,观察到Blue-Ⅰ引起MCG803细胞核呈典型的凋亡形态;经流式细胞仪分析,2.5,5和10mg·L-1的Blue-Ⅰ处理24h,凋亡细胞率分别由对照组的(3.5±0.6)%上升为(11.4±3.5)%,(32.4±4.9)%和(50.7±6.6)%。Blue-Ⅰ还能导致MCG803周期细胞比例发生改变。结论Blue-Ⅰ具有抑制胃腺癌细胞增殖的作用,其机制可能主要是通过诱导肿瘤细胞凋亡。AIM To study whether Blue-Ⅰ [3- [ 1,2-dihydro-5-（ 5-hydroxy-1 H-indol-3-yl-） -2- oxo-2h-pyrrol-3-ylidene ]-1, 3-dihydro-2H-indol-2-one], a metabolic product from a new marine species, Rhodomarinobacter spp. inhibits proliferation of human gastric cancer cells （MCG803）. METHODS The IC50 of Blue- Ⅰ on MCG803 was determined by MTT test. DNA damage was detected by single cell electrophoresis. Apoptosis cells and the cell cycles of tumor cells were analyzed by Hoechst 33258 staining and by flow cytometer assay. RESULTS The MCG803 cell proliferation was inhibited by Blue-Ⅰ and the IC50 was （4. 6 ± 1.1 ） mg· L^-1. The degradation of the genome of the apoptotic cells induced by the Blue-Ⅰ was also detected. The percentage of tailed cells were （23.2 ±4.9）% , （51.4 ±6.9）% and （68.7 ± 6.5 ） % in the groups containing 2.5, 5 and 10 mg· L^-1 of Blue-Ⅰ, respectively, while （4.2 ± 1.2 ） % in the control group. The average tail length increased with the concetrations of Blue- Ⅰ detected with comet assay. When MCG803 cells were treated with 2.5 - 10 mg·L^-1 Blue- Ⅰ for 24 h, the typical apoptotic nuclear morphological changes were observed with Hoechst 33258 staining. The ratios of the apoptotic cells were （ 11.4 ± 3.5 ） % , （ 32.4±4.9 ）% and （50.7 ±6.6）% in the groups containing 2.5, 5 and 10 mg·L^-1 of Blue-Ⅰ respectively, as compared with （ 3.5± 0.6） % in the untreated group. Flow cytometry assay indicated that the cell cycles of the tumor cells were also altered by the compound. CONCLUSION Blue-Ⅰ could effectively suppress the gastric cancer cells proliferation. The mechanism perhaps involved in the apoptosis of gastric cancer cells induced by Blue- Ⅰ.

关 键 词：紫色色杆菌素类 Blue-Ⅰ 海洋细菌 胃肿瘤 细胞凋亡 DNA损伤 

分 类 号：R735.2[医药卫生—肿瘤]