二噁英对成骨肉瘤细胞增殖和胰岛素样生长因子2表达的影响  

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on cell proliferation and insulin-like growth factor 2 in osteogenic sarcoma cells

作　　者：赵玉岩[1] 郭磊[1] 都健[1] 马冬杰[1] 田蕾[1] 

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

出　　处：《中国药理学与毒理学杂志》2008年第4期296-300,共5页Chinese Journal of Pharmacology and 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项目(05L508);辽宁省教育厅高等学校科学研究项目(20061010)~~

摘　　要：目的探讨环境类致癌因子二噁英（TCDD）对成骨肉瘤细胞增殖及胰岛素样生长因子2（IGF-2）mRNA和蛋白表达的影响。方法TCDD作用于人成骨肉瘤细胞SaOS-2细胞株24-48h。MTT法检测细胞增殖率;对硝基酚磷酸盐法测定细胞内碱性磷酸酶（ALP）活性;RT-PCR半定量分析细胞IGF-2 mRNA的表达;Western蛋白质印迹法测定细胞IGF-2和丝裂原激活蛋白激酶（MAPK）信号通路中p38 MAPK蛋白表达及其磷酸化水平。结果与对照组比较,TCDD 1,10和100nmol·L^-1作用48h,使SaOS-2细胞内ALP活性分别增加38%,95%和142%。TCDD 1,10及100nmol·L^-1作用24h后,SaOS-2细胞存活率分别增加21%,47%和56%,细胞内IGF-2 mRNA和IGF-2蛋白表达均增加。TCDD对SaOS-2细胞内p38 MAPK蛋白表达无明显影响,但明显降低其磷酸化水平。结论TCDD具有促进SaOS-2细胞增殖的作用。TCDD可能通过促进SaOS-2细胞内IGF-2的表达,并抑制MAPK信号通路中转录因子p38 MAPK活性而促进细胞增殖。AIM To investigate the effects of environmental carcinogenic factor 2,3,7,8-tetrachlorodibenzo-p-dioxin （TCDD） on cell proliferation and expression of insulin-like growth factor 2 （IGF-2） in osteogenic sarcoma （ SaOS-2 ） cells. METHODS SaOS-2 Cells were treated with TCDD for 24 -48 h. MTT assay was used to detect cell proliferation. Alkaline phosphatase （ALP） activity in SaOS-2 cells was measured using the nitrophenol phosphate salt method. IGF-2 mRNA level in SaOS-2 cells was detected by reverse transcription polymerase chain reaction （RT-PCR）. IGF-2 protein, p38 mitogen-activated protein kinase （p38 MAPK） and phospho-p38 MAPK（P-p38 MAPK） levels were detected by Western blot analysis. RESULTS Treated with TCDD 1, 10 and 100 nmol·L^-1for 48 h ALP activity in SaOS-2 cells was increased about 38% , 95% and 142%, respectively, compared with control group. Treated with TCDD 1, 10 and 100 nmol·L^-1 for 24 h, cell proliferation increasedabout 21%, 47% and 56%, respectively, and the expressions of IGF-2 mRNA and protein in SaOS-2 cells increased. TCDD did not affect the protein expression of p38 MAPK in MAPK signal pathway, but decreased the P-p38 MAPK level in SaOS-2 cells. CONCLUSION TCDD may increase proliferation of SaOS-2 cells, which may be related with its enhancement of IGF-2 expression, and inhibition of p38 MAPK activity.

关 键 词：二噁英 细胞增殖 骨肉瘤 胰岛素样生长因子2 信号传导通路 

分 类 号：R738.1[医药卫生—肿瘤]