bFGF表达对裸鼠白血病移植瘤血管新生影响的研究

  目的   研究丙戊酸钠（VPA）对裸鼠白血病细胞移植瘤血管新生的影响，并探讨其作用机制。  方法  使用白血病细胞株Kasumi-1细胞接种于裸鼠皮下，建立裸鼠白血病细胞移植瘤模型，分为对照组和VPA治疗组进行研究，免疫组织化学标记肿瘤组织血管内皮细胞的CD34，计算微血管密度。RT-PCR、蛋白印迹和免疫组织化学检测碱性成纤维细胞生长因子（bFGF）mRNA表达水平及蛋白含量水平。  结果  对裸鼠白血病移植瘤研究发现，VPA治疗14 d后，裸鼠瘤组织CD34+血管内皮细胞明显减少，微血管密度（MVD）为32.59±5.76较对照组12.23±4.11明显减少（P < 0.01）；VPA治疗组bFGF mRNA的表达0.321±0.046较对照组0.151±0.036明显降低（P < 0.01），bFGF蛋白表达为0.493±0.026较对照组0.298±0.011明显下降。  结论  VPA可以抑制裸鼠白血病细胞移植瘤的血管新生，其发生的机制与抑制血管新生相关因子bFGF的表达有关。 

Effects of bFGF expression on the angiogenesis of a leukemia cell line transplanted into nude mice

  Objective  This study aimed to investigate the antiangiogenesis of valproic acid (VPA) in leukemia cell line-transplanted tumor in nude mice and to explore the mechanisms of VPA.   Methods   A nude mice model with xenograft tumor was established by the subcutaneous inoculation of Kasumi-1 cells. The mice were randomly assigned to control and VPA-treated groups. CD34 expression was assessed by immunohistochemistry. Basic FGF mRNA and protein levels were quantified by RT-PCR, Western blot analysis, and immunohistochemistry.   Results   After 2 weeks of treatment with VPA, in the VPA-treated group, CD34 expression and the calculated MVD markedly decreased (P < 0.01). After treatment with VPA, the mRNA (0.321 ± 0.046) and protein (0.493 ± 0.026) levels of bFGF also significantly reduced (P < 0.01) compared with the mRNA (0.151 ± 0.136; P < 0.01) and protein (0.298 ± 0.011; P < 0.01) levels of the control group.   Conclusion  VPA induced the antiangiogenesis of the leukemia cell line-transplanted tumor in nude mice. The mechanism of action may include the inhibition of bFGF expression.