کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3446413 1595474 2014 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Alteration of the Intrinsic Apoptosis Pathway Is Involved in Notch-induced Chemoresistance to Gemcitabine in Pancreatic Cancer
ترجمه فارسی عنوان
تغییر مسیر آپوپتوز درگیر در مقاومت شیمیایی ناشی از قطعه به گمسیتابین در سرطان پانکراس است
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی پزشکی و دندانپزشکی (عمومی)
چکیده انگلیسی

Background and AimsChemoresistance is a major challenge in pancreatic cancer (PC) treatment. Limited data have shown that members of the Notch signaling pathway are involved in resistance to gemcitabine (GEM) in PC. However, further evidence is needed and the underlying mechanisms remain to be elucidated. The current study aims to investigate the role of alterations of the intrinsic apoptosis pathway in Notch-induced GEM resistance of PC.MethodsThe Notch signaling pathway was inhibited or activated in three PC cell lines (AsPC-1, BxPC-3, and MIA PaCa-2) by γ-secretase inhibition and Notch intracellular domain (NICD) overexpression, respectively. Subsequent analyses included inhibition rates of cell proliferation by GEM, cell apoptosis, and expression of proteins involved in the intrinsic apoptosis pathway.ResultsHes-1 expression was significantly elevated after GEM treatment, indicating Notch activation. Inhibition of the Notch signaling pathway by DAPT, a γ-secretase inhibitor, resulted in a significant increase of the inhibition rates by GEM in all PC cell lines. In addition, there was more frequent apoptosis, higher caspase-3 activity, up-regulation of Bax, and down-regulation of Bcl-2 and Bcl-xL. Conversely, transient transfection of NICD, which enhances the activity of the Notch signaling, caused a remarkable decrease of the chemosensitivity to GEM.ConclusionsAn alteration of the intrinsic apoptosis pathway is involved in Notch-induced chemoresistance to GEM in PC cells.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Archives of Medical Research - Volume 45, Issue 1, January 2014, Pages 15–20
نویسندگان
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