As2O3抑制人淋巴瘤Raji细胞增殖及VEGF表达

本研究探讨在As2O3作用下人淋巴瘤Raji细胞的增殖及VEGF mRNA表达的变化.采用改良MTT方法观察As2O3对Raji细胞的增殖抑制效应;采用半定量RT-PCR方法检测As2O3对Raji细胞VEGF121和VEGF165 mRNA表达的影响.结果表明As2O3对Raji细胞的作用表现时间、剂量依赖性的增殖抑制效应,建立回归方程为IR＝0.531dose+0.481time(P＜0.05).半定量RT-PCR方法检测显示,Raji细胞同时表达VEGF121和VEGF165两种剪切变异体,二者的表达水平相当(VEGF1211.17±0.14;VEGF1651.31±0.19,P＞0.05).VEGF121和VEGF165 mRNA表达量与As2O3作用时间呈负相关关系(rsv121=-0.547,P＜0.05;rsv165=-0.632,P＜0.05),且VEGF的各异构体对药物的反应具有差异性,VEGF165 mRNA表达下调早且有持续性.但在所选浓度组中未发现类似的相关关系(P＞0.05).结论As2O3既可抑制Raji细胞生长增殖,亦可通过下调VEGF mRNA表达而产生抗血管新生效应,且小剂量、长时程给药时结果亦然.

Inhibited Proliferation of B-lymphoma Raji Cells and Down-regulated Expression of VEGF by Arsenic Trioxide

This study was aimed to investigate the effects of As2O3 on proliferation of B lymphoma Raji cell and to study the expression changes of VEGF mRNA. The modified MTT was adopted to evaluate the effect of As2O3 on proliferation of Raji cells. Semi-quantitative RT-PCR was used to detect the expression of VEGF121 and VEGF165 mRNA in Raji cells exposed to As2O3. The results showed that the As2O3 significantly inhibited the proliferation of Raji cells, the relationship between the inhibition rate and the concentrations of As2O3 was dose- and time-dependent. The VEGF121 and VEGF165 mRNA expressions were found in Raji cells, and both were well-matched in expression levels. After treatment of As2O3 at 1 micromol/L for 48 hours, the expression levels of VEGF121 and VEGF165 mRNA were significantly down-regulated and demonstrated negative correlation with the time of exposure to As2O3. Otherwise some difference were observed in effects of As2O3 on VEGF121 and VEGF165, the expression of VEGF165 mRNA was down-regulated earlier and longer than that of VEGF121, while no similar correlation was found in selected concentration groups. It is concluded that As2O3 can significantly inhibit the growth of Raji cells and may exerted its anti-angiogenesis effects by down-regulating the VEGF mRNA expression even in a low concentration for a long term.