کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10814876 | 1058428 | 2015 | 48 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
HSP90 inhibitor NVP-AUY922 enhances TRAIL-induced apoptosis by suppressing the JAK2-STAT3-Mcl-1 signal transduction pathway in colorectal cancer cells
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کلمات کلیدی
PBSSDSPARP-1TNFRPMITumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)PAGENVP-AUY922polyacrylamide gel electrophoresis - الکتروفورز ژل پلی آکریل آمیدApoptosis - خزان یاختهایsodium dodecyl sulfate - سدیم دودسیل سولفاتtumor necrosis factor - فاکتور نکروز تومورTRAIL - قطارtumor necrosis factor-related apoptosis-inducing ligand - لیگاند ناشی از آپوپتوز وابسته به عامل بیماری تومورphosphate-buffered saline solution - محلول نمک فسفات بافرRoswell Park Memorial Institute medium - موسسه خاطرات Roswell Park mediumwild type - نوع وحشیHeat shock protein 90 (Hsp90) - پروتئین شوک حرارت 90 (Hsp90)Propidium iodide - پروتئین یدیدpoly (ADP-ribose) polymerase-1 - پلی (ADP-ribose) پلیمراز-1
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: HSP90 inhibitor NVP-AUY922 enhances TRAIL-induced apoptosis by suppressing the JAK2-STAT3-Mcl-1 signal transduction pathway in colorectal cancer cells HSP90 inhibitor NVP-AUY922 enhances TRAIL-induced apoptosis by suppressing the JAK2-STAT3-Mcl-1 signal transduction pathway in colorectal cancer cells](/preview/png/10814876.png)
چکیده انگلیسی
TRAIL has been shown to induce apoptosis in cancer cells, but in some cases, certain cancer cells are resistant to this ligand. In this study, we explored the ability of representative HSP90 (heat shock protein 90) inhibitor NVP-AUY922 to overcome TRAIL resistance by increasing apoptosis in colorectal cancer (CRC) cells. The combination of TRAIL and NVP-AUY922 induced synergistic cytotoxicity and apoptosis, which was mediated through an increase in caspase activation. The treatment of NVP-AUY922 dephosphorylated JAK2 and STAT3 and decreased Mcl-1, which resulted in facilitating cytochrome c release. NVP-AUY922-mediated inhibition of JAK2/STAT3 signaling and down-regulation of their target gene, Mcl-1, occurred in a dose and time-dependent manner. Knock down of Mcl-1, STAT3 inhibitor or JAK2 inhibitor synergistically enhanced TRAIL-induced apoptosis. Taken together, our results suggest the involvement of the JAK2-STAT3-Mcl-1 signal transduction pathway in response to NVP-AUY922 treatment, which may play a key role in NVP-AUY922-mediated sensitization to TRAIL. By contrast, the effect of the combination treatments in non-transformed colon cells was minimal. We provide a clinical rationale that combining HSP90 inhibitor with TRAIL enhances therapeutic efficacy without increasing normal tissue toxicity in CRC patients.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 27, Issue 2, February 2015, Pages 293-305
Journal: Cellular Signalling - Volume 27, Issue 2, February 2015, Pages 293-305
نویسندگان
Dae-Hee Lee, Ki Sa Sung, David L. Bartlett, Yong Tae Kwon, Yong J. Lee,