کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1940090 1050773 2006 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Knockdown of hypoxia-inducible factor-1α in breast carcinoma MCF-7 cells results in reduced tumor growth and increased sensitivity to methotrexate
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Knockdown of hypoxia-inducible factor-1α in breast carcinoma MCF-7 cells results in reduced tumor growth and increased sensitivity to methotrexate
چکیده انگلیسی

The hypoxia-inducible factor (HIF) 1α is a key regulator of the cellular response to oxygen deprivation. Specific disruption of the HIF-1 pathway is important for exploring its role in tumor biology and developing more efficient weapons to treat cancer. In this study, we stably transfected human breast tumor MCF-7 cells with short hairpin RNA expression vectors targeting HIF-1α. After knockdown of HIF-1α, hypoxia-induced expression of its target genes such as vascular endothelial growth factor, Glut-1, phosphoglycerate kinase, and P-glycoprotein were markedly attenuated. Moreover, HIF-1α knockdown was found to suppress the shift from S-phase to G1 induced by hypoxia and increase drug sensitivity to methotrexate. The growth rates of HIF1α-knockdown tumors were drastically retarded in both subcutaneous and orthotopic xenograft models, which were accompanied by decreased angiogenesis and reduced expression of glucose transporter in tissue sections. These data demonstrate that HIF-1α knockdown reduces tumorigenicity of MCF-7 cells and suggest a promising combination of both anti-HIF-1 strategy and traditional chemotherapy to improve cancer treatment.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 342, Issue 4, 21 April 2006, Pages 1341–1351
نویسندگان
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