ArticleExperimental and therapeutic medicine2012
Interferon-γ enhances promyelocytic leukemia protein expression in acute promyelocytic cells and cooperates with all-trans-retinoic acid to induce maturation of NB4 and NB4-R1 cells.
Article in Experimental and therapeutic medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 8 citations in OpenAlex.
- PLZF-RARCancers · 2020Review
- Combination of enzastaurin and ATRA exerts dose-dependent dual effects on ATRA-resistant acute promyelocytic leukemia cells.American journal of cancer research · 2019Article
- Article
- Combined staurosporine and retinoic acid induces differentiation in retinoic acid resistant acute promyelocytic leukemia cell lines.Scientific reports · 2014Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In order to investigate the effect and mechanisms of interferon (IFN)-γ in combination with all-trans-retinoic acid (ATRA) on NB4 cells [ATRA-sensitive acute promyelocytic leukemia (APL) cell line] and NB4-R1 cells (ATRA-resistant APL cell line) and to search for a novel approach to solve the problem of ATRA resistance in APL, we initially treated NB4 and NB4-R1 cells with IFN-γ, ATRA and IFN-γ in combination with ATRA, respectively. The cell proliferation was then tested by MTT assay, and the cell differentiation was tested through light microscopy, by NBT test and flow cytometry (FCM). The expression of promyelocytic leukemia (PML) protein was observed by indirect immune fluorescent test. Results showed that ATRA inhibited the growth of NB4 cells, however, it could not inhibit the growth of NB4-R1 cells. IFN-γ inhibited the growth of both NB4 and NB4-R1 cells. Meanwhile, the growth inhibition effect of IFN-γ in combination with ATRA on both NB4 and NB4-R1 cells was significantly stronger than that of any single drug treatment. The results of the NBT reduction test and CD11b antigen detection by FCM indicated that IFN-γ induces the differentiation of NB4 and NB4-R1 cells to some extent. Moreover, the maturation degree of both NB4 and NB4-R1 cells induced by IFN-γ in combination with ATRA was more significant than that of IFN-γ or ATRA alone. After treatment with IFN-γ, the number of fluorescent particles in NB4 and NB4-R1 cell nuclei was higher than those in the control group, which indicated that IFN-γ may induce the expression of PML protein. Together, IFN-γ augments the proliferation inhibition effect of ATRA on NB4 and NB4-R1 cells through enhancing the expression of PML protein. IFN-γ in combination with ATRA not only strengthens the induction differentiation effect of ATRA on NB4 cells, but also can partially induce the maturation of NB4-R1 cells with ATRA resistance.
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Registered trials
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