کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5527705 | 1547885 | 2017 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Research paperArtesunate induces apoptosis via inhibition of STAT3 in THP-1 cells Research paperArtesunate induces apoptosis via inhibition of STAT3 in THP-1 cells](/preview/png/5527705.png)
- AML patients had higher expression of STAT3 than that of the controls.
- ART inhibited the growth of THP-1 cells and xenografts in nude mice.
- ART down-regulated the expression of STAT3 in THP-1 cells and tumour tissues of mice.
- ART can induce THP-1 cell apoptosis, and further analyses showed that ART can activate caspase-3 and caspase-8.
ObjectiveOur objective was to explore STAT3 expression in patients with acute myeloid leukaemia (AML), assess the anti-proliferative effects of artesunate (ART) on THP-1 cells in vivo and in vitro, and investigate the underlying mechanisms.MethodsIn this study, we examined 30 patients with acute myeloid leukaemia diagnosed in our hospital from January 2015 to January 2016. The 20 control group patients had non-haematological diseases and were hospitalized for the same period. We extracted 2 ml bone marrow, separated the mononuclear cells, obtained total proteins, and detected STAT3 protein levels with Western blot analyses. The THP-1 cells were treated with different concentrations of ART(0, 10, 25, 50, 100, 200 μM). Then, THP-1 cell viability was detected with CCK-8 assays, apoptosis was measured with flow cytometry, and the STAT3, caspase-3 and caspase-8 protein levels were assessed using Western blot analyses. THP-1 cells in logarithmic growth phase were subcutaneously injected into the necks of 5-week-old nude mice. The control group was subcutaneously injected with 0.1 ml PBS. After the nude mouse tumours grew, the mice were divided into the control group and drug intervention groups (ART 100 μM group, ART 200 μM group). The mice in the intervention groups were intraperitoneally injected with ART, and the control group was injected with the same amount of normal saline. Then, changes in the tumours were observed. After the drug intervention, the total protein was extracted, and STAT3 expression was detected by Western blot analysis.ResultsCompared with the control group, the AML patients had significantly increased STAT3 protein levels (P < 0.01). ART significantly inhibited the proliferation of THP-1 cells in a dose-dependent and time-dependent manner. ART also increased THP-1cell apoptosis. After treatment with ART, STAT3 protein was significantly down-regulated, and apoptosis of the cells was induced by the activation of caspase-3 and caspse-8.ConclusionAML patients had higher expression of STAT3 than that of the controls. ART induced apoptosis in THP-1 cells and inhibited the growth of xenografts in nude mice, and we also observed that ART down-regulated the expression of STAT3 and activated the caspase-3 and caspase-8. We speculated that the effect of ART on THP-1 cells may be related to inhibition of STAT3 and activation of caspase3 and caspase-8.
Journal: Leukemia Research - Volume 62, November 2017, Pages 98-103