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目的 探讨组蛋白脱乙酰化酶 (HDAC)抑制剂苯丁酸钠 (PB)联合 5 氮杂脱氧胞苷 (5 Aza CdR)对t(8;2 1)急性髓系白血病裸鼠移植瘤模型的抑瘤活性与作用机制。方法 用Kasumi 1细胞皮下接种的方法建立t(8;2 1)急性髓系白血病裸鼠移植瘤模型 ;观察裸鼠的致瘤潜伏期、PB预处理Kasumi 1细胞的致瘤性改变 ,以及PB和 5 Aza CdR腹腔注射对移植瘤生长的抑制作用。流式细胞术检测细胞分化抗原和细胞周期 ,末端脱氧核糖核酸转移酶介导的dUTP原位缺口末端标记 (TUNEL)检测瘤组织凋亡 ,免疫组织化学染色检测血管新生。结果 切脾和不切脾裸鼠接种Kasumi 1细胞后致瘤潜伏期分别为 17～ 2 3d和 4 0～ 5 0d ,瘤细胞不转移 ,仍检测出t(8;2 1)和AML1 ETO融合基因。接种PB预处理Kasumi 1细胞的裸鼠未见成瘤。PB、5 Aza CdR单独或联合裸鼠体内用药后 ,移植瘤生长抑制率分别为 4 9.0 7%、2 5 .6 9%和 87.4 6 % (P <0 .0 5 ) ,凋亡细胞指数分别为 (2 .2 5± 0 .85 ) %、(1.32± 0 .6 8) %和 (5 .4 1± 1.5 6 ) % (P <0 .0 5 ) ,微血管密度 (MVD)分别为 2 1.6 9± 6 .2 5 ,2 8.34± 4 .2 4和 9.4 8± 3.2 1(P <0 .0 1) ,与对照组相比有显著性差异 (P值均 <0 .0 5 )。PB腹腔注射后移植瘤细胞CD11b、CD13表达增高 [(12 .0 8±
Objective To investigate the effect of HDA inhibitor sodium phenylbutyrate (PBAC) combined with 5-azacytidine (5 Aza CdR) on the tumor model of t (8; 21) acute myeloid leukemia in nude mice Anti-tumor activity and mechanism. Methods The nude mouse model of acute myeloid leukemia was established by subcutaneous inoculation with Kasumi 1 cells. The tumorigenic potential of Kasumi 1 cells treated with PB was observed. 5 Aza CdR intraperitoneal injection on the growth inhibition of tumor. Flow cytometry was used to detect cell differentiation antigen and cell cycle. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) was used to detect the apoptosis of tumor tissue. Immunohistochemical staining was used to detect angiogenesis. Results The tumorigenicity of Kasumi 1 cells was 17 ~ 2 3d and 40 ~ 50d after inoculation of Kasumi 1 cells. The tumor cells did not metastasize and the t (8; 2 1) and AML1 ETO fusion genes were still detected . Nude mice inoculated with PB pretreated with Kasumi 1 cells showed no tumorigenesis. The inhibitory rates of tumor growth of PB and 5 Aza CdR alone or in combination with nude mice were 44.0%, 25.69% and 87.4% (P <0.05), respectively. The apoptotic index (2.25 ± 0.85)%, (1.32 ± 0.68)% and (5.14 ± 1.56)% (P <0.05) respectively. The microvessel density (MVD) was 2 1.6 9 ± 6 .2 5, 2 8.34 ± 4 .2 4 and 9.4 8 ± 3.2 1 (P <0.01), which were significantly different from the control group (all P <0.05). After intraperitoneal injection of PB, the expression of CD11b and CD13 in tumor cells increased [(12.0 ± 8)%]