摘要
目的探讨环境外源性污染物三-(2,3-二溴丙基)异氰脲酸酯(TBC)诱导人肝癌细胞株HepG2凋亡的死亡受体途径。方法采用MTT法、流式细胞术确定TBC对HepG2细胞的毒性作用、细胞凋亡率,Western blot法对死亡受体信号通路关键蛋白Caspase-8、FADD、CD95/FAS、DR4、DR5、PARP和TRAIL的蛋白水平表达进行检测。结果TBC处理浓度增加(0、12.5、25和50)μg/ml对HepG2细胞的增殖抑制作用增强,凋亡峰越明显,表明DNA合成受到抑制。且细胞内PARP蛋白表达量逐渐降低,细胞内的Caspase-8、FADD、CD95/FAS、DR4、DR5和TRAIL蛋白表达量逐渐升高,呈现剂量-效应关系。结论环境外源性污染物TBC具有细胞毒性,且可以通过死亡受体途径进行诱导细胞凋亡,为其他外源性化合物的毒理学研究和早期干预提供了理论基础。
Objective To determine the cytotoxicity and apoptosis-inducing effects of exogenous tri-(2,3-dibromopropyl)isocyanurate(TBC)on human hepatocyte cell HepG2 via the death receptor pathway.Methods Toxicology of TBC on HepG2 cells and apoptosis rate were detected by MTT assay,inverted microscope,fluorescence microscope,flow cytometry,the expressions of key proteins Caspase-8,FADD,CD95/FAS,DR4,DR5,PARP and TRAIL in death receptor signaling pathway were detected by Western blot assay.Results As the increasing of TBC expose doses(0,12.5,25,50)μg/ml of TBC,inhibition of proliferation of HepG2 and apoptotic peaks were more obvious,which indicated that DNA synthesis inhibited enhanced.The expressions of PARP protein in cells decreased,the expression of Caspase-8、FADD、CD95/FAS、DR4、DR5 and TRAIL protein increased,which appeared a dose effect relationship.Conclusion Environmental exogenous pollutant TBC has cytotoxicity and can induce apoptosis via death receptor pathway,which provides a theoretical basis for toxicological studies and early intervention of other exogenous compounds.
作者
綦峥
韩馥蕊
乐志威
冯雅杰
杨明
李金龙
QI Zheng;HAN Fu-rui;LE Zhi-wei;FENG Ya-jie;YANG Ming;LI Jin-long(Engineering Research Center for Medicine,Harbin University of Commerce,Harbin Heilongjiang 150076,China)
出处
《毒理学杂志》
CAS
CSCD
2021年第4期311-315,321,共6页
Journal of Toxicology
基金
黑龙江省自然科学基金(LH2019D007)
黑龙江省省属高等学校基本科研业务费资助项目(2020CX09,2020CX10,2020CX38)
中央支持地方高校改革发展基金优秀青年人才项目(2020YQ12)。
