کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5552915 1557951 2017 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Overexpression of heme oxygenase-1 in bone marrow stromal cells promotes microenvironment-mediated imatinib resistance in chronic myeloid leukemia
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی تومور شناسی
پیش نمایش صفحه اول مقاله
Overexpression of heme oxygenase-1 in bone marrow stromal cells promotes microenvironment-mediated imatinib resistance in chronic myeloid leukemia
چکیده انگلیسی

Neoplasm cells from patients with chronic myeloid leukemia (CML) interact with stromal cells of the surrounding microenvironment. Bone marrow stromal cells (BMSCs) represent the main population in CML marrow stroma, which may play a key role in disease support and progression. Heme oxygenase-1 (HO-1) is a key enzyme of antioxidative metabolism that is associated with cell proliferation and resistance to apoptosis. We herein up-regulated HO-1 expression of BMSCs and evaluated whether BMSCs influenced K562 cells survival. BMSCs were isolated from the bone marrow of normal people and CML patients. Following co-culture of BMSCs and K562 cells, up-regulating HO-1 expression in bone marrow stromal cells increased the imatinib (IM) resistance of K562 cells, whereas the apoptosis of K562 cells was effectively promoted without BMSCs co-culture. The protection may be mediated by CXCL12 (stromal derived factors 1, SDF-1)/CXCR4 signaling. The CXCL12/CXCR4 interaction significantly enhanced the phosphorylation of AKT. As far as drug resistance was concerned, BMSCs counteracted the cytotoxic effect of IM administration in vitro, and they protected K562 cells from the apoptosis induced by kinase inhibitor IM. The regulated HO-1 expression of BMSCs provides a new putative target for CML therapy.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomedicine & Pharmacotherapy - Volume 91, July 2017, Pages 21-30
نویسندگان
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