کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1936981 1050706 2007 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Jak inhibitor induces S phase cell-cycle arrest and augments TRAIL-induced apoptosis in human hepatocellular carcinoma cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Jak inhibitor induces S phase cell-cycle arrest and augments TRAIL-induced apoptosis in human hepatocellular carcinoma cells
چکیده انگلیسی

Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in various cancers and plays a crucial role in oncogensis, including the activation of genes encoding apoptosis inhibitors and cell-cycle regulators. We investigated the biological significance of the Janus kinase (Jak)-STAT pathway in human hepatocellular carcinoma (HCC). Constitutive activation of STAT3 was seen in 49.4% of human HCC specimens and in HCC cell lines. Jak inhibitor AG490 inhibited activation of STAT3 and markedly reduced cell viability without significant apoptosis. AG490 also induced S phase cell-cycle arrest with down-regulation of cyclin D1, A, E and up-regulation of p21, p27, phospho-Chk2. AG490 also inhibited caspase inhibitory proteins, such as XIAP and survivin, and augmented TRAIL-induced apoptosis. Our study suggests that the Jak-STAT pathway plays an important role in cell-cycle progression and resistance to apoptosis. Inhibition of the Jak-STAT pathway may thus be a therapeutic target for HCC.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 363, Issue 3, 23 November 2007, Pages 738–744
نویسندگان
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