He Peng-Cheng, Zhang Mei, Li Jing, Cao Yun-Xin, Cai Rui-Bo, Liu Ya-Lin
Department of Hematology, First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, China.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2007 Mar;23(3):205-8.
To explore the possibility and the possible mechanism of reversing ATRA-resistance in MR2 cells by using IFN-alpha and IFN-gamma in combination with all-trans retinoic acid (ATRA).
After MR2 cells(ATRA-resistance cell line) were treated with IFN-alpha, IFN-gamma and ATRA alone or IFN-alpha and IFN-gamma in combination with ATRA respectively, the cell proliferation was tested by MTT colorimetry, the cell differentiation was tested through light microscope, by NBT test and flow cytometry (FCM). The expression of promyelocytic leukemia (PML) protein was observed by indirect immunofluorescence staining.
Both IFN-alpha and IFN-gamma could inhibit the proliferation of MR2 cells. The effects were more obviously in both IFN-alpha+ATRA group and IFN-gamma+ATRA group. But there were no significant difference between either IFN-alpha group and IFN-gamma group or IFN-alpha+ATRA group and IFN-gamma+ATRA group (P>0.05). Both IFN could also induce the differentiation of MR2 cells. The effects of IFN-alpha+ATRA group and IFN-gamma+ATRA group were more obvious. However, the differentiation of MR2 cells induced by IFN-gamma+ATRA group was more higher than that by IFN-alpha+ATRA group (P<0.05). Both IFN could induce the expression of PML protein.
The reversing effcet of IFN-gamma+ATRA group on ATRA-resistence in MR2 cells are more powerful than that of IFN-alpha+ATRA group, which may be related to the different signal transduction pathway of IFN-alpha and IFN-gamma.
探讨联合使用干扰素-α(IFN-α)、干扰素-γ(IFN-γ)与全反式维甲酸(ATRA)逆转MR2细胞对ATRA耐药的可能性及可能机制。
将MR2细胞(ATRA耐药细胞系)分别用IFN-α、IFN-γ、ATRA单独处理,以及IFN-α和IFN-γ分别与ATRA联合处理后,采用MTT比色法检测细胞增殖,通过光学显微镜、硝基蓝四唑(NBT)试验和流式细胞术(FCM)检测细胞分化。采用间接免疫荧光染色观察早幼粒细胞白血病(PML)蛋白的表达。
IFN-α和IFN-γ均可抑制MR2细胞增殖。IFN-α+ATRA组和IFN-γ+ATRA组的抑制作用更明显。但IFN-α组与IFN-γ组之间以及IFN-α+ATRA组与IFN-γ+ATRA组之间均无显著差异(P>0.05)。两种干扰素也均可诱导MR2细胞分化。IFN-α+ATRA组和IFN-γ+ATRA组的诱导作用更明显。然而,IFN-γ+ATRA组诱导MR2细胞的分化程度高于IFN-α+ATRA组(P<0.05)。两种干扰素均可诱导PML蛋白表达。
IFN-γ+ATRA组对MR2细胞ATRA耐药的逆转作用强于IFN-α+ATRA组,这可能与IFN-α和IFN-γ不同的信号转导途径有关。