کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8435210 | 1546686 | 2016 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
GSK-3 inhibition overcomes chemoresistance in human breast cancer
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کلمات کلیدی
absorption, distribution, metabolism, excretion, toxicityGLPGSK-3CDKPKCADMETpKaAkt - آکتind - اندرGood Laboratory Practice - تمرین خوب آزمایشگاهیDrug development - توسعه داروییInvestigational New Drug - داروهای جدید تحقیقاتیBreast cancer - سرطان پستانpharmacokinetic - فارماکوکینتیکprotein kinase A - پروتئین کیناز Aprotein kinase B - پروتئین کیناز BProtein kinase C - پروتئین کیناز سیChemoresistance - کمروییcyclin-dependent kinase - کییناز وابسته به سیکلین
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Glycogen Synthase Kinase-3β (GSK-3β), a serine/threonine protein kinase, is an emerging therapeutic target in the treatment of human breast cancer. In this study, we demonstrate that the pharmacological inhibition of GSK-3 by two novel small molecule GSK-3 inhibitors, 9-ING-41 and 9-ING-87, reduced the viability of breast cancer cells but had little effect on non-tumorigenic cell growth. Moreover, treatment with 9-ING-41 enhanced the antitumor effect of irinotecan (CPT-11) against breast cancer cells in vitro. We next established two patient-derived xenograft tumor models (BC-1 and BC-2) from metastatic pleural effusions obtained from patients with progressive, chemorefractory breast cancer and demonstrated that 9-ING-41 also potentiated the effect of the chemotherapeutic drug CPT-11 in vivo, leading to regression of established BC-1 and BC-2 tumors in mice. Our results suggest that the inhibition of GSK-3 is a promising therapeutic approach to overcome chemoresistance in human breast cancer, and identify the GSK-3 inhibitor 9-ING-41 as a candidate targeted agent for metastatic breast cancer therapy.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 380, Issue 2, 1 October 2016, Pages 384-392
Journal: Cancer Letters - Volume 380, Issue 2, 1 October 2016, Pages 384-392
نویسندگان
Andrey Ugolkov, Irina Gaisina, Jin-San Zhang, Daniel D. Billadeau, Kevin White, Alan Kozikowski, Sarika Jain, Massimo Cristofanilli, Francis Giles, Thomas O'Halloran, Vincent L. Cryns, Andrew P. Mazar,