地塞米松对三氧化二砷诱导淋巴瘤细胞凋亡与NF-κB活化及相关基因表达的影响

目的　研究三氧化二砷(As2O3 )诱导淋巴瘤细胞凋亡与核因子κB(NF κB)活化以及血管内皮生长因子(VEGF)、基质金属蛋白酶9(MMP9)表达的关系,并观察地塞米松(Dex)抑制NF κB活化对As2O3诱导淋巴瘤细胞凋亡及VEGF、MMP9表达的影响。方法　采用流式细胞仪AnnexinⅤFITC法检测Raji细胞凋亡;采用免疫组织化学方法半定量分析Raji细胞NF κB、VEGF、MMP9表达的动态变化。结果　As2O3同时具有诱导Raji细胞凋亡凋亡率为(39. 2±1. 3)% ]和NF κB活化的作用; 1. 0μmol/LDex能显著增加1 . 0μmol/LAs2O3诱导Raji细胞凋亡(增加率为77. 5%,P<0. 05)和抑制As2O3诱导Raji细胞NF κB活化(抑制率为28. 0%,P<0. 05)的作用,VEGF、MMP9变化与NF κB一致。结论　As2O3诱导Raji细胞凋亡的同时活化NF κB,VEGF、MMP9表达亦随之增强;Dex在抑制As2O3诱导Raji细胞NF κB活化的同时增强其诱导细胞凋亡的作用,VEGF、MMP9的表达也相应下降。

Effects of dexamethasone on arsenic trioxide induced apoptosis, NF-κB activation and gene expression in lymphoma cell line

OBJECTIVES: To study the effect of dexamethasone (Dex) on the apoptosis and NF-kappaB activation in Raji cells as well as expression of MMP9 and VEGF induced by As2O3, and to observe the effect of inhibited activity of NF-kappaB by Dex on apoptosis. METHODS: Cell apoptosis was analysed by Annexin V. Fluctuation of NF-kappaB, MMP9 and VEGF was detected by semi-quantitative immunohistochemistry. RESULTS: The apoptosis and activation of NF-kappaB of Raji cells could be induced by As2O3. The percentage of apoptosis was (39.2 +/- 1.3)%. Dex significantly increased (77.5%) the apoptosis induced by As2O3 (P < 0.05). Dex suppressed the activation of NF-kappaB induced by As2O3 (a suppression rate of 28.0%, P < 0.05). There was a positive correlation between the changes of MMP9, VEGF and NF-kappaB. CONCLUSIONS: As2O3 could induce apoptosis, activate NF-kappaB and up-regulate expression of MMP9 and VEGF of Raji cells. The mechanism of enhanced apoptosis by Dex may be related to suppressing activation of NF-kappaB and down-regulating expression of MMP9 and VEGF.