聚酯型儿茶素对HL-60细胞的诱导分化作用及其机制研究

目的　研究聚酯型儿茶素对人急性早幼粒白血病HL 6 0细胞的分化作用并探讨其作用机制。方法　应用电镜、NBT还原试验、同位素掺入试验、细胞内cAMP/cGMP浓度测定、原位杂交和免疫细胞化学等方法研究细胞分化及机制。结果　聚酯型儿茶素作用于HL 6 0细胞后 ,扫描电镜和透射电镜观察显示分化细胞的特征 ;NBT还原能力明显增强 ;3H] TdR ,3H] Leu掺入试验证明聚酯型儿茶素可明显抑制细胞DNA和蛋白质合成 ;聚酯型儿茶素作用后 ,细胞内cAMP浓度及cAMP/cGMP比值明显增加 ,HL 6 0细胞的c myc基因mRNA和蛋白产物的表达均明显降低 ,而c fos基因mRNA和蛋白产物的表达均明显升高。结论　聚酯型儿茶素可诱导HL 6 0细胞向成熟细胞分化 ,其分化作用可能与其升高细胞内cAMP/cGMP比值和抑制c myc基因表达、增强c fos基因表达有关。本研究为聚酯型儿茶素在肿瘤防治领域的开发应用提供了充分的理论依据

Induction of differentiation and its mechanism by theasinesin in HL 60 cells

AIM To investigate the induction of differentiation and its mechanism by theasinesin in human promyelocytic leukemia cell line (HL 60). METHODS Electronic microscopy technique, NBT reduction test, 3H TdR, 3H Leu incorporation test, determination of the intracellular cAMP and cGMP level, in situ hybridization and immunocytochemistry were used to identify cell differentiation. RESULTS After HL 60 cells were treated with theasinesin, cell differentiation was identified by scanning electronic microscopy and transmission electronic microscopy.The reduction of NBT in HL 60 cells was obviously increased. Theasinesin could strongly inhibit DNA and protein synthesis and increase intracellular cAMP levels or cAMP/cGMP ratios. C myc expression was significantly decreased and c fos increased strongly in a dose dependent manner. CONCLUSION Theasinesin can induce differentiation of HL 60 cells. Its mechanisms may involve the elevation of cAMP/cGMP ratio, expression inhibition of c myc gene and expression enhancement of c fos gene.