二噁英对成骨肉瘤细胞中胰岛素样生长因子2基因表达的作用  

Effect of dioxin on gene expression of insulin-like growth factor 2 in osteogenic sarcoma cells

作　　者：赵玉岩[1] 郭磊[2] 田蕾[1] 张世亮[2] 刘魁[2] 

机构地区：[1]中国医科大学附属第一医院内分泌科,辽宁沈阳110001 [2]中国医科大学附属第一医院骨科,辽宁沈阳110001

出　　处：《毒理学杂志》2008年第5期342-344,共3页Journal of Toxicology

基　　金：国家自然科学基金资助项目(30500414);辽宁省教育厅高等学校科学研究资助项目(20061010)

摘　　要：目的探讨环境类致癌因子对调控成骨肉瘤细胞中胰岛素样生长因子2(insulin-like growth factor 2,IGF-2)基因表达的作用机制。方法应用环境类致癌因子二噁英(TCDD)作用于人成骨肉瘤细胞(SaOS-2)细胞株;采用流式细胞仪检测TCDD对SaOS-2细胞凋亡的影响规律;采用实时定量PCR定量分析SaOS-2细胞中IGF-2 mRNA的表达;采用Western印迹杂交鉴定SAOS-2细胞中IGF-2和促分裂原活化蛋白激酶(MAPK)信号通路中的p38 MAPK蛋白质的表达及磷酸化水平的变化。结果1×10-9mol/L、1×10-8mol/L、1×10-7mol/L剂量的TCDD对SaOS-2细胞具有抗凋亡作用,在基因转录和翻译水平上增强SaOS-2细胞中IGF-2的表达;TCDD明显地降低了SaOS-2细胞内p38 MAPK磷酸化水平。结论低生理浓度的TCDD可促进靶基因IGF-2的表达,并通过p38 MAPK信号转导通路,发挥拮抗成骨细胞凋亡的毒性作用。Objective To investigate the regulation of environmental carcinogenic factor-2,3,7,8-tetrachlorodibenzo-p-dioxin （TCDD） on gene expression of insulin-like growth factor 2 （IGF-2） in osteogenie sarcoma （SaOS-2） cells. Methods Cell apoptosis in SaOS-2 cells treated with TCDD（ 1×10^-9 mol/L, 1 × 10 ^-8 mol/L, 1 × 10^-7 mol/L） was detected by flow cytometry. IGF-2 mRNA level in SaOS-2 cells was detected by real-time reverse transcription polymerase chain reaction （PCR）, and its protein and phosphorylation of p38 MAPK （mitogen-activated protein kinase） were detected by western blotting analysis. Results The rate of cell apoptosis treated with TCDD at 1 × 10^-9 mol/L, 1 ×10^-8 mol/L, 1× 10^-7mol/L concentration decreased about 5% , 26%and 52% , respectivily. Gene transcription and translation of IGF-2 were increased in TCDD-treated SaOS-2 cells. TCDD did not affect the protein expression of p38 MAPK in MAPK signal pathway, but down-regulated the phosphorylation tevel of p38 MAPK in SaOS-2 cells. Conclusion TCDD may be up-regnlated the gene expression of IGF-2 in SaOS-2 cells. The activity of p38 MAPK in SaOS-2 cells was inhibited by TCDD.

关 键 词：二噁英 肿瘤细胞 胰岛素样生长因子2 信号通路 

分 类 号：R344.13[医药卫生—基础医学] R273