کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10754632 | 1050359 | 2014 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The novel mTORC1/2 dual inhibitor INK-128 suppresses survival and proliferation of primary and transformed human pancreatic cancer cells
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کلمات کلیدی
PI3KS6 kinase 1PBMNCsAkt/mTor signaling4E-binding proteinmTOR complex 2mTORC2mTORC14E-BP1S6K1mTORFACSmTOR complex 1 - mTOR پیچیده 1MTT - MTTImmunoprecipitation - تخریب ایمنیfluorescence-activated cell sorting - دسته بندی سلول های فعال فلورسنسPancreatic cancer - سرطان پانکراسperipheral blood mononuclear cells - سلول های تک هسته ای خون محیطیphosphoinositide 3-kinase - فسفینوزیتید 3-کینازmammalian target of rapamycin - هدف پستانداران رپامایسینPropidium iodide - پروتئین یدیدoptical density - چگالی نوری
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Pancreatic cancer has one of worst prognosis among all human malignancies around the world, the development of novel and more efficient anti-cancer agents against this disease is urgent. In the current study, we tested the potential effect of INK-128, a novel mammalian target of rapamycin (mTOR) complex 1 and 2 (mTORC1/2) dual inhibitor, against pancreatic cancer cells in vitro. Our results demonstrated that INK-128 concentration- and time-dependently inhibited the survival and growth of pancreatic cancer cells (both primary cells and transformed cells). INK-128 induced pancreatic cancer cell apoptosis and necrosis simultaneously. Further, INK-128 dramatically inhibited phosphorylation of 4E-binding protein 1 (4E-BP1), ribosomal S6 kinase 1 (S6K1) and Akt at Ser 473 in pancreatic cancer cells. Meanwhile, it downregulated cyclin D1 expression and caused cell cycle arrest. Finally, we found that a low concentration of INK-128 significantly increased the sensitivity of pancreatic cancer cells to gemcitabine. Together, our in vitro results suggest that INK-128 might be further investigated as a novel anti-cancer agent or chemo-adjuvant for pancreatic cancer treatment.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 450, Issue 2, 25 July 2014, Pages 973-978
Journal: Biochemical and Biophysical Research Communications - Volume 450, Issue 2, 25 July 2014, Pages 973-978
نویسندگان
Hai-zhou Lou, Xiao-chuan Weng, Hong-ming Pan, Qin Pan, Peng Sun, Li-li Liu, Bin Chen,