کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8463921 | 1549407 | 2013 | 40 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Enhanced anticancer efficacy of snake venom combined with silica nanoparticles in a murine model of human multiple myeloma: Molecular targets for cell cycle arrest and apoptosis induction
ترجمه فارسی عنوان
کارآیی ضد سرطانی پیشرفته از سم مار در ترکیب با نانوذرات سیلیکا در یک مدل موشی از چندین میلوما انسانی: اهداف مولکولی برای توقف چرخه سلولی و القاء آپوپتوز
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کلمات کلیدی
IL-6Bcl-2CKRSROS - ROSinterleukin-6 - اینترلوکین ۶Proliferation - ترویجApoptosis - خزان یاختهایSnake venom - زهر مارB-cell lymphoma 2 - لنفوم سلول B 2Multiple myeloma - مولتیپل میلوماMyeloma - میلوماNanoparticles - نانوذراتChemokine - کموکاین یا کموکین Reactive oxygen species - گونههای فعال اکسیژنChemokine receptors - گیرنده های شیمیایی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
چکیده انگلیسی
Multiple myeloma (MM) is a clonal disease of plasma cells that reside in the bone marrow (BM). MM is an incurable disease; thus, screening for novel anti-myeloma drugs remains critically important. We recently described a silica nanoparticle-based snake venom delivery model that targets cancer cells, but not normal cells. Using this model, we demonstrated a strong enhancement of the antitumor activity of snake venom extracted from Walterinnesia aegyptia (WEV) in two breast carcinoma cell lines when the venom was combined with silica nanoparticles (WEVÂ +Â NP). In the present study, we aimed to delineate the in vivo therapeutic efficacy of WEVÂ +Â NP in an MM-bearing experimental nude mouse model. We found that treatment with WEVÂ +Â NP or WEV alone significantly inhibited tumor growth compared to treatment with NP or vehicle. WEVÂ +Â NP- and WEV-treated cancer cells exhibited marked elevations in oxidative stress and robust reductions in the levels of interleukin-6 (IL-6) and B cell-activating factor (BAFF). WEVÂ +Â NP also decreased the surface expression of the chemokine receptors CXCR3, CXCR4 and CXCR6 to a greater extent than WEV alone, and WEVÂ +Â NP subsequently reduced migration in response to the cognate ligands CXCL10, CXCL12 and CXCL16. Furthermore, we found that WEVÂ +Â NP strongly inhibited insulin-like growth factor 1 (EGF-1)- and IL-6-mediated MM cell proliferation, altered the cell cycle and enhanced the induction of apoptosis of MM cells. In addition, the results of treatment with WEVÂ +Â NP or WEV alone revealed that the combination of WEV with NP robustly decreased the expression of cyclin D1, Bcl-2 and the phosphorylation of AKT; increased the expression of cyclin B1; altered the mitochondrial membrane potential; increased the activity of caspase-3, -8 and -9; and sensitized MM cells to growth arrest and apoptosis. Our data reveal the therapeutic potential of the nanoparticle-sustained delivery of snake venom to fight cancer cells.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Immunology - Volume 284, Issues 1â2, JulyâAugust 2013, Pages 129-138
Journal: Cellular Immunology - Volume 284, Issues 1â2, JulyâAugust 2013, Pages 129-138
نویسندگان
Mohamed K. Al-Sadoon, Danny M. Rabah, Gamal Badr,