组蛋白脱乙酰化酶抑制剂对Kasumi-1细胞血管新生相关因子表达的影响

目的 研究组蛋白脱乙酰化酶(HDAC)抑制剂丙戊酸钠(VPA)及曲古菌素(TSA)对白血病细胞系Kasumi-1细胞血管内皮生长因子(VEGF)、VEGF受体(KDR或FLK-1)及碱性成纤维细胞生长因子(bFGF)表达的影响,探讨其抗白血病血管新生的可能机制.方法 采用RT-PCR及Western blot方法 分析不同浓度VPA、TSA处理Kasumi-1细胞3 d后VEGF及其受体KDR mRNA及蛋白水平的变化,RT-PCR检测bFGF mRNA水平的变化.结果 VPA能够下调VEGF mRNA(3 mmol/L时处理组VEGF121 0.034±0.004、VEGF165 0.015±0.001,对照组分别为0.632±0.014、0.526±0.021)、KDRmRNA(3 mmol/L组0.038±0.000对0.258±0.034)及蛋白的表达,下调bFGF mRNA(3 mmol/L组0.086±0.015对0.228±0.017)的表达;TSA对VEGF、KDR mRNA及蛋白表达的影响与VPA相似,较高浓度的TSA能够下调bFGF mRNA的表达.结论 HDAC抑制剂可能通过调节血管新生相关因子及受体的表达,阻碍白血病患者的血管新生,从而抑制白血病的进展.

Effects of histone deacetylase inhibitor on the expression of angiogenesis related factors in Kasumi-1 leukemic cell line

Objective To investigate the effects of two histone deacetylase( HDAC) inhibitors, valp-roic acid(VPA) and TSA, on the expression of vascular endothelial growth factor (VEGF) and its receptor KDR of the leukemia cell line Kasumi-1 cells, and to explore their potential mechanism in leukemia angiogenesis. Method Kasumi-1 cells were treated with VPA and TSA at different concentrations for 3 days. The mRNA and protein expression levels of VEGF and KDR were determined by semi-quantitative RT-PCR and Western blot, and the bFGF mRNA by semi-quantitative RT-PCR. Results As compared with that of control groups, VPA at 3 mmol/L downregulated the VEGF mRNA expression level for VEGF121 from 0.632 0.014 to 0.034 0.004 and for VEGF165 from 0. 526 0. 021 to 0. 015 0. 001, for KDR mRNA from 0. 258 0.034 to 0.038 0.000, and for bFGF mRNA from 0.228 0.017 to 0. 086 0. 015. TSA downregulated the VEGF mRNA and KDR mRNA at concentration of 100 nmol/L, but its effect on bFGF mRNA only at higher concentration. Conclusion HDAC inhibitors might inhibit the leukemia angiogenesis by regulating the expression of VEGF and its recptor.