کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8434091 | 1546634 | 2018 | 43 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Co-inhibition of BET and proteasome enhances ER stress and Bim-dependent apoptosis with augmented cancer therapeutic efficacy
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Co-inhibition of BET and proteasome enhances ER stress and Bim-dependent apoptosis with augmented cancer therapeutic efficacy Co-inhibition of BET and proteasome enhances ER stress and Bim-dependent apoptosis with augmented cancer therapeutic efficacy](/preview/png/8434091.png)
چکیده انگلیسی
Agents that inhibit bromodomain and extra-terminal domain (BET) protein have been actively tested in the clinic as potential anticancer drugs. Proteasome inhibitors such as carfilzomib (CFZ) are FDA-approved for the treatment of patients with advanced multiple myeloma and have been tested against other cancers. The current study focuses on the combination of a BET inhibitor (e.g., JQ1) and a proteasome inhibitor (e.g., CFZ) as a novel cancer therapeutic strategy and the underlying mechanisms. The tested combination (JQ1 with CFZ) synergistically decreased cell survival and enhanced apoptosis in vitro and inhibited tumor growth in vivo. The dramatic induction of apoptosis was accompanied by enhanced elevation of Bim and ER stress. Bim knockout significantly attenuated apoptosis induced by the combination, suggesting a critical role of Bim induction in mediating the enhanced induction of apoptosis by BET and proteasome co-inhibition. The combination significantly increased Bim mRNA levels with limited effect on Bim protein stability, suggesting a primary transcriptional regulation of enhanced Bim expression. Our findings warrant further investigation of this combinatorial strategy as an effective regimen against cancer in the clinic.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 435, 28 October 2018, Pages 44-54
Journal: Cancer Letters - Volume 435, 28 October 2018, Pages 44-54
نویسندگان
Guoqing Qian, Weilong Yao, Shuo Zhang, Richa Bajpai, Williams D. Hall, Mala Shanmugam, Sagar Lonial, Shi-Yong Sun,