Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D02003 (NBT)
 1,323 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to explore the effect of N, N'-di-(m-methylphenyi)-3, 6-dimethyl-1, 4-dihydro-1, 2, 4, 5-tetrazine-1, 4-dicarboamide (ZGDHu-1) on proliferation, differentiation and apoptosis in NB4 human leukemia cell line and its possible mechanism. Different concentrations of ZGDHu-1 and the different time of cultivation were used to treat NB4 cells. The proliferation inhibition of NB4 cells was analysed by cell counting, alive cell count, MTT assay. Cell apoptosis was determined by cell morphology, DNA agarose gel electrophoresis, DNA content, Annexin-V/PI and Hoechst 33258 labeling method. The analysis of cell morphological change, expression of CD11b, CD13 and NBT reduction were performed to evaluate the differentiation of NB4 cells. The expressions of bcl-2, bax and phosphorylated p38MAPK or STAT3 were detected by flow cytometry. While the expression of hTERT mRNA in transcriptional level was measured by fluorescence quantitative RT-PCR. The results showed that ZGDHu-1 could inhibit NB4 cell proliferation viability within a certain range of treating time and does, IC(50) values at 48 and 72 hours were 450 ng/ml and 200 ng/ml respectively. A majority of NB4 cells were arrested in G(2/M) phase and a progressive decline of cells was seen in G(0/1). The NB4 cells apoptosis was confirmed by cell typical cell morphology, DNA fragments and sub-G(1) phase peak as well as Hoechst33258 and Annexin-V/PI labeling method with a time-dose-related manner. The morphology of NB4 cells cultured in the presence of 2 - 100 ng/ml ZGDHu-1 for three days was more mature with higher NBT positivity and expressions of CD11b and CD13 than those in control. The expression of phosphor-p38MAPK and bax was increased while phosphor-STAT3 and bcl-2 were unchanged by the treatment of ZGDHu-1. ZGDHu-1 could decrease the expression of hTERT-mRNA in a dose-dependent manner. It is concluded that ZGDHu-1 can inhibit proliferation, induce differentiation and apoptosis of NB4 cells. The mechanism may be associated with up-regulation of bax expression, enhancement of phosphor-p38MAPK activation and inhibition of hTERT-mRNA.
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PMID:[Effects of N, N'-Di-(m-methylphenyi)-3, 6-dimethyl-1, 4-dihydro-1, 2, 4, 5-tetrazine-1, 4-dicarboamide on proliferation, apoptosis and differentiation of NB4 leukemia cells in vitro]. 1709 81

The aim of this study was to observe the effect of p38MAPK inhibitor SB203580 on ATRA-induced differentiation of NB4 cells. The proliferation activity of cells was assayed by MTT method, the cell cycle was detected by flow cytometry, the differentiation of NB4 cells into granulocytes was measured by test of NBT reduction, the activity of extracellular signal-regulated kinase (ERK) was detected by substrate phosphorylation. The results showed that the ATRA in 0.01-01 micromol/L inhibited the proliferation of NB4 cells in time-and dose-dependent manner and induced the differentiation of NB4 cells into myeloid; the ATRA stimulated ERK activity in this process; ERK inhibitor PD98059 could partially block ATRA effect, specific inhibitor of p38MAPK, SB203580, combined with ATRA also could partially block the effects of ATRA on inhibition of NB4 growth and induction of differentiation. It is concluded that the ATRA stimulates ERK and p38MAPK pathway in the process inducing differentiation of NB4 cells, the ERK and P38MAPK may be necessary for the ATRA-induced differentiation in NB4 cells.
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PMID:[Effect of mitogen-activated protein kinases on ATRA-induced differentiation of NB4 cells]. 1909 31