کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8293057 1536741 2018 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
AZD5153, a novel BRD4 inhibitor, suppresses human thyroid carcinoma cell growth in vitro and in vivo
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
AZD5153, a novel BRD4 inhibitor, suppresses human thyroid carcinoma cell growth in vitro and in vivo
چکیده انگلیسی
The development of novel anti-papillary thyroid carcinoma agents is urgent. AZD5153 is a novel and specific Bromodomain-containing protein 4 (BRD4) inhibitor. Here, we show that AZD5153 dose-dependently inhibited survival, proliferation and cell cycle progression in TPC-1 cells and primary human thyroid carcinoma cells. Yet, it was non-cytotoxic to the primary thyroid epithelial cells. AZD5153 induced caspase-3/-9 and apoptosis activation in TPC-1 cells and primary cancer cells. Its cytotoxicity in TPC-1 cells was significantly attenuated with co-treatment of the caspase inhibitors. BRD4 expression was elevated in TPC-1 and primary human thyroid carcinoma cells, but was low in the thyroid epithelial cells. BRD4-regulated proteins, including c-Myc, Bcl-2 and cyclin D1, were significantly downregulated following AZD5153 treatment in TPC-1 and primary cancer cells. In vivo, oral administration of AZD5153 at well-tolerated doses significantly inhibited TPC-1 xenograft growth in severe combined immunodeficient (SCID) mice. BRD4-dependent proteins, Myc, Bcl-2 and cyclin D1, were also downregulated in AZD5153-treated tumor tissues. Collectively, the results suggest that targeting BRD4 by AZD5153 inhibits human thyroid carcinoma cell growth in vitro and in vivo.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 499, Issue 3, 15 May 2018, Pages 531-537
نویسندگان
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