Effects of varied interferons in combination with all-trans retinoic acid (ATRA) on proliferation and differentiation of ATRA-resistent APL cell

摘要

Objective: To investigate the effects and mechanisms of interferon in combination with all-trans retinoic acid (ATRA) on proliferation and differentiation of ATRA-resistent APL cell. Methods:After MR_2 cells (ATRA-resistance cell line) were treated with IFN-α, IFN-γ and ATRA alone or IFN-α and IFN-γ in combination with ATRA respectively. The cell proliferation was tested by MTT test and 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 immune fluorescent method. Results: Both IFN-α and IFN-γ could inhibit the proliferation and induce the differentiation of MR_2 cells to some extent. The effects were more obvious after both interferons in combination with ATRA respectively (P < 0.05). Moreover, the maturation of MR_2 cells induced by IFN-γ + ATRA group was more higher than that by IFN-α + ATRA group (P < 0.05). Both interferons could induce the expressions of PML protein. Conclusion: Both interferons can inhibit MR_2 cells proliferation, which may be related to the expression of PML protein induced by both interferons. The inducing differentiation effects of IFN-γ + ATRA group on MR_2 cells are more powerful than those of IFN-α + ATRA group, which may be related to the different signal transduction pathway of both interferons.