The impact of At1r inhibition via losartan on the anti-leukaemic effects of doxorubicin in acute myeloid leukaemia
Date
2019Author
Ghasemi, Mehdi and Okay, Mufide and Turk, Seyhan and Naeemaee, Ronak and
Guver, Ebru and Malkan, Umit Y. and Aksu, Salih and Sayinalp, Nilgun and
Haznedaroglu, Ibrahim C.
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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.
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