γ—干扰素合并维甲酸对维甲酸耐药细胞的作用机制

In Vitro Study of the Effects of IFNγ with ATRA on ATRA-Resistant Promyelocytic Cell Line

目的寻求解决维甲酸 (ATRA)耐药问题的新途径。 方法光镜、NBT还原实验及免疫荧光间接法观察NB4及其耐药细胞MR - 2单用及联用ATRA、γ -干扰素 (IFNγ)后细胞形态学、细胞分化及PML蛋白表达的变化。 结果IFNγ单用及与ATRA联用对两种细胞的生长均有抑制作用 ,IFNγ能诱导PML蛋白的表达 ,ATRA与IFNγ联用能部分诱导耐药细胞分化 结论IFNγ通过诱导PML蛋白的表达而抑制细胞生长 ,ATRA与IFNγ联用部分诱导耐药细胞分化的作用可能与两药各自不同的信号传递途径发生交叉激活有关。

Objective To find new ways to deal with the problem of retinoid resistance. Methods Observation under light microscope, NBT test and indirect fluorescence immunoassay. Results 1.IFNγ alone or combined with ATRA suppresses the growth rate of NB4 as well as MR-2 and high dose IFNγ exerts greater suppression;2.PML expression is induced by IFNγ;3.the combination of ATRA and IFNγ partially induces differentiation of the ATRA-resistant promyelocytic cell line. Conclusion IFNγ induces the expression of PML, a growth suppressor and an anti-oncogene, which in consequence suppresses the cell growth. The combined differentiative effect of ATRA and IFNγ on ATRA -resistant cell MR-2 might be due to the cross talk between the signal pathways of ATRA and IFNs.