کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5525323 1546670 2017 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Original ArticleTherapeutic effects of Argyrin F in pancreatic adenocarcinoma
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Original ArticleTherapeutic effects of Argyrin F in pancreatic adenocarcinoma
چکیده انگلیسی


- We investigated the effects of Argyrin F (AF) in a model of pancreatic cancer (PC).
- AF therapy inhibited proliferation, migration, invasion and induced apoptosis.
- AF therapy blocked tumor growth, neo-vascularization and metastasis in mice with PC.
- Mechanistically, AF stabilized p27kip, up-regulated p21waf1/cip1 and depleted COX2.
- AF treatment might evolve as a new therapeutic approach to treat patients with PC.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with limited treatment options. The proteasome inhibitor Argyrin A, a cyclic peptide derived from the myxobacterium Archangium gephyra, shows antitumoral activities. We hypothesize that his analogue Argyrin F (AF) may also prevent PDAC progression. We have used PDAC cells and engineered mice (Pdx1-Cre; LSL-KrasG12D; p53 lox/+) to assess AF anticancer activity. We analyzed the effect of AF on proliferation and epithelial plasticity using MTT-, wound healing-, invasion-, colony formation-, apoptosis-, cell cycle- and senescence assays. In vivo treatment with AF, Gemcitabine (G) and combinational treatment (AF + G) was performed for survival analysis. AF inhibited cell proliferation, migration, invasion and colony formation in vitro. AF impaired epithelial-mesenchymal transition (EMT), caused considerable apoptosis and senescence in a dose- and time-dependent manner and affected cell cycle G1/S phase transition. G treatment achieved longest mice survival, followed by AF + G and AF compared to vehicle group. However, AF + G treatment induced the largest reduction in tumor spread and ascites. In conclusion, we have demonstrated that AF prevents PDAC progression and that combined therapy was superior to AF monotherapy. Therefore, AF treatment might be useful as an additional therapy for PDAC.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 399, 28 July 2017, Pages 20-28
نویسندگان
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