FK228对TNFα诱导人肝癌细胞HepG2凋亡及核因子κB活化的影响

Effects of FK228 on apoptosis and activation of NF-κB Induced by TNFα in human hepatoma cell line HepG2

目的研究FK228对TNFα诱导的人肝癌细胞HepG2凋亡及核转录因子κB(nuclear factor-κB,NF-κB)活化的影响。方法培养HepG2细胞分别用TNFα刺激和FK228+TNFα共同作用,westernblot分析细胞核中NF-κBp65及其细胞浆中抑制因子IκBα的表达;用流式细胞技术测定细胞凋亡。结果组蛋白去乙酰化酶抑制剂FK228(4～32ng/mL)能抑制TNFα诱导的NF-κBp65的核转移,减少胞浆中IκBα的降解,且增强TNFα诱导的细胞凋亡。结论FK228减少胞浆中IκBα降解、抑制NF-κB的活化可能是诱导HepG2细胞凋亡、发挥抗肿瘤作用的重要机制。

[Objective] To investigate the effect of FK228 on the TNFα-induced apoptosis and activation of NF-κBp65 in human hepatoma cell line HepG2. [Methods] Cultured HepG2 were divided into 3 groups, namely, normal control group, TNFα stimulation group, and interference group（FK228＋TNFα）. The expression of NF-κBp65 in nuclear and IκBα in the cytosolic were measured by western blot. Cell apoptosis was detected by flow cytomery. [Results] FK228 （4-32ng/mL）not only inhibited TNFα-induced nuclear translocation of NF-κBp65 but also reduced degradation of IκBα and enhanced TNFet-induced cell apoptosis. [Conclusion] The inhibition of FK228 on activation of NF-κB by reducing degradation of IκBα may is a critical mechanism for the HepG2 cell apoptosis and anti-tumor activity.