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      The impact of At1r inhibition via losartan on the anti-leukaemic effects of doxorubicin in acute myeloid leukaemia

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      Author(s)
      Ghasemi, M.
      Okay, M.
      Türk, S.
      Naeemaee, Ronak
      Güver, Ebru
      Malkan, Ü. Y.
      Aksu, S.
      Sayınalp, N.
      Haznedaroğlu, I. C.
      Date
      2019-05
      Source Title
      Journal of the Renin-Angiotensin-Aldosterone System
      Print ISSN
      1470-3203
      Electronic ISSN
      1752-8976
      Publisher
      Sage Publications
      Volume
      20
      Issue
      2
      Pages
      1 - 9
      Language
      English
      Type
      Article
      Item Usage Stats
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      86
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      Abstract
      Introduction: Bone marrow renin–angiotensin system(RAS) modulates acute myeloid leukaemia(AML).The aim of this study is to clarify the relationships between RAS and AML, and to show the effect of losartan and doxorubicin treatment in AML cell lines. Methods: AML cell lines including CESS, HL-60, MO-1, P31/FUJ, GDM-1 and KASUMI-3 were used as models in this study. Results:After treating the six AML cell lines with a combination of losartan and doxorubicin, they were divided into two groups based on their behaviour: one became more sensitive to drug treatment (Group A) and the other had no change observed in behaviour after drug treatment (Group B). In silico analyses showed that Group A is involved in cellular apoptosis, while Group B is involved in tumour angiogenesis further supporting the in vitro results. Conclusion:The combined treatment of the AML cell lines with losartan and doxorubicin resulted in an increase in sensitivity of some of the cell lines. Those leukaemic cells are modulated via the induction of apoptosis, whereas the other cells resistant to the drug treatment are closely related to tumour angiogenesis indicating that RAS-AT1R seems to be differently expressed in different leukaemic blast cells and tumour microenvironments. Pharmaco-biological actions of RAS inhibitors may be different in distinct leukaemic cells based on the pathological behaviour of AML genomic subtypes.
      Keywords
      RAS
      AML
      AT1R
      AT2R
      ANG II
      Losartan
      Doxorubicin
      Drug combination
      Permalink
      http://hdl.handle.net/11693/53426
      Published Version (Please cite this version)
      https://dx.doi.org/10.1177/1470320319851310
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