TNF-α诱导脑胶质瘤细胞凋亡过程中NF-κB、IκB活性的研究

Study of biological activation of NF-κB、IκB in apoptosisof brain glioma U251 induced by TNF-α

目的探讨核转录因子-κB(NF-κB)及其抑制因子(IκB)在肿瘤坏死因子-α(TNF-α)诱导人脑胶质瘤细胞株U 251细胞凋亡过程中生物活性的变化。方法应用流式细胞仪检测TNF-α对U-251细胞生长的抑制和诱导凋亡作用。用免疫组化方法检测肿瘤细胞p65的表达,用W estern b lot检测IκB蛋白的变化。结果TNF-α可诱导U 251细胞凋亡,激活细胞中p65并诱导IκB降解;抗氧化剂二硫碳吡咯烷醇(PDTC)可抑制TNF-α诱导的IκB的降解及NF-κB的激活,增强TNF-α诱导U 251细胞的凋亡。结论TNF-α在诱导U 251细胞凋亡的过程中可激活NF-κB。抑制NF-κB活性,可增强TNF-α诱导细胞凋亡的作用。

Objective： To study the changes of biological activation of NF-κB. ⅠκB in apoptosis of U-251 induced by TNF-α. Method, Apotosis was detected by Flow cytometry. The expression of NF-κB. ⅠκB was determined by immunohistochemical and Western Blot. Rseuh.. TNF-α could inhibit the gowth of U251 and after its administration,p65 was activated and ⅠκB expression decreased. PDTC could markedly increase the sensitivity of U251 to TNF-α and suppress the activation of NF-κB through attenuating the decrease of ⅠκB. Conclusion.. The resistance of U251 towards apoptosis induced by TNF-α can be mediated by NF-κB activation. The inhibition the activation of NF-κB can attenuate the resistance and increase its sensitivity to TNF-α.