地塞米松和长春新碱抑制核因子-κB活化增强高三尖杉酯碱诱导K562-n细胞凋亡

摘要

Objective: To explore the effects of dexamethasone (DXM) and vincristine (VCR) on apoptosis andactivation of nuclear factor-κ-gene binding (NF-κB) in leukemic cell line K562-n induced byhomoharringtonine (HH). Methods: Apoptosis of K562-n cells was analysed by TdT-mediated X-dUTP nickand end labeling (TUNEL) and DNA electrophoresis. NF-κB activity of K562-n cells was detected byelectrophoretic mobility shift assay (EMSA). Results: There was slight activation of NF- κ B evident in K562-nceils even without induced by drugs. HH at 0.5 μ mol/L significantly increased the activation of NF- κ B inK562-n cells. The level of NF- κ B activation induced by DXM at 1 μ mol/L or VCR at 0.1μ mol/L indicatedno significant difference when compared with that of the control group. However, in K562-n cells pre-treatedwith 1 μ mol/L of DXM or 0.1 μ mol/L of VCR, the activation of NF- κ B induced by 0.5 μ mol/L of HH wassignificantly suppressed with inhibitory rates of 32.0% and 39.4%, respectively. The apoptosis rates of K562-ncells induced by 0.5 μ mol/L, 5.0 μ mol/L, 50 μ mol/L HH were 30.00% ± 3.34%, 47.13%± 3.18%, 68.63% ±8.14%, respectively. The apoptotic rate K562-n cells induced by DXM at 1 μ mol/L or VCR at 0.1 μ mol/Lwere similar to that of the control group. However, either DXM at 1 μ mol/L or VCR at 0.1 μ mol/L couldincrease the apoptosis of K562-n cells induced by HH at 0.5 μ mol/L at rates of 85.8% and 114.6%, respectively.Conclusion: HH could induced apoptosis and activation of NF-κB in K562-n cells. The mechanism of increasedapoptosis by DXM or VCR might be related to suppression of NF-κB activity in K562-n cells.%目的:研究地塞米松(DXM)和长春新碱(VCR)对高三尖杉酯碱(HH)诱导白血病细胞系K562-n凋亡与核因子-κB(NF-κ B)活化的影响.方法:采用TdT介导的dUTP缺口末端标记技术(TUNEL)、DNA电泳方法观察K562-n细胞凋亡.采用电泳迁移率变动分析(EMSA)观察K562-n细胞NF-κB活化.结果:K562-n细胞未经药物诱导NF-κB有轻度活化;HH 0.5μmol/L可明显诱导K562-n细胞NF-κB活化,DXM 1.0 μ mol/L和VCR 0.1μmol/L能显著抑制HH0.5 μmol/L诱导的NF-κB活化,抑制率分别为32.0%和39.4%(P均＜0.05).HH 0.5、5、50μmol/L均能诱导K562-n细胞凋亡,凋亡率分别为(30.00±3.34)%、(47.13±3.18)%和(68.63±8.14)%.DXM 1.0μmol/L和VCR 0.1 μmol/L本身无诱导K562-n细胞凋亡的作用,但均能增强HH0.5μmol/L诱导的K562-n细胞凋亡,凋亡率分别提高达85.8%和114.6%(P均＜0.05).结论:HH诱导K562-n细胞凋亡的同时激活NF-κB;DXM和VCR可通过抑制NF-κB活化,增强其诱导K562-n细胞凋亡的作用.