摘要
目的:探讨血管内皮生长因子(vascu-larendothelialgrowthfactor,VEGF)对白血病细胞生物学特性的影响。方法:台盼蓝拒染实验观察VEGF对白血病细胞增殖的影响,流式细胞术检测VEGF对化疗药物阿糖胞苷(Ara-C)所诱导的白血病细胞凋亡和胞内抗凋亡蛋白bcl-2表达的影响,用集落形成方法观察VEGF对白血病祖细胞增殖的影响。结果:50ng/mLVEGF作用白血病细胞24h,活细胞数为(3·63±1·27)×106mL-1,与阴性对照(3·23±1·60)×106mL-1差异无统计学意义。VEGF可以抵抗Ara-C200ng/mL诱导白血病细胞的凋亡。白血病细胞胞内bcl-2蛋白的阳性表达(70·78±13·36)%明显高于正常对照组(18·55±9·24)%,P=0·039。VEGF可显著延缓细胞内bcl-2表达。VEGF组:(50·85±30·46)%,阴性对照:(36·52±12·38)%。VEGF促进非红系(白血病)集落的形成。VEGF组:(49·9±29·2)/0·5mL,阴性对照:(36·5±12·4)/0·5mL,P=0·013;VEGF对红系和混合集落形成无明显影响。结论:VEGF能抵抗化疗药物Ara-C所致的白血病细胞凋亡,并促进白血病细胞集落的形成,以VEGF为AML治疗靶点可望改善患者的预后。
OBJECTIVE:To investigate the effect of vascular endothelial growth factor (VEGF) on acute myeloid leukemic cells. METHODS: Cell proliferation was detected by the trypan blue exclusion assay, the apoptosis and concentration of intracellular bcl-2 protein by flow cytometry, and the number of cells colonies by the colony-forming assay. RESULTS: The living cells number in VEGF group, which was (3.63± 1.27) × 10^6 mL^-1 was not significantly different from the negative controls (3.23±1.60)× 10^6 mL^-1. The protein level of intracellular bcl-2 in leukaemic cells group ( 70.78± 13.36) % was muchs higher than that in the normal controls (18. 55± 9.24) %, P= 0. 039; so was the intracellular bcl-2-incubation with VEGF (50.85 ± 30.46)% compared with the controls (36.52± 12.38)%. The percentage of apoptotic cells induced by Ara-C was much more than that in leukemic cells incubated with VEGF group. The number of non-erythroid colonies (49.9±29.2)/0.5 mL, with VEGF was much more than that of the control (36.5±12.4)/0.5 mL, P=0.013. VEGF did not up regulate the number of mix-colonies, but VEGF promoted the proliferation of AML stem/progenitor ceils. CONCLUSIONS: VEGF can resist leukemic cell apoptosis induced by Ara-C and promote leukemic stem/progenitor ceils. Therefore, VEGF, as a novel thoraperatic target, can improve therapy outcome in AML.
出处
《中华肿瘤防治杂志》
CAS
2006年第14期1089-1091,1094,共4页
Chinese Journal of Cancer Prevention and Treatment