کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3902978 1250372 2010 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Potent Cytotoxic Effect of a Novel Nuclear Factor-κB Inhibitor Dehydroxymethylepoxyquinomicin on Human Bladder Cancer Cells Producing Various Cytokines
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های کلیوی
پیش نمایش صفحه اول مقاله
Potent Cytotoxic Effect of a Novel Nuclear Factor-κB Inhibitor Dehydroxymethylepoxyquinomicin on Human Bladder Cancer Cells Producing Various Cytokines
چکیده انگلیسی

ObjectivesTo explore the potential therapeutic effects of the nuclear factor-κB (NF-κB) inhibitor dehydroxymethylepoxyquinomicin (DHMEQ). KU-19-19 cells, originally derived from a patient with invasive bladder cancer who exhibited marked leukocytosis, produce multiple cytokines. This model of clinically advanced bladder cancer, in which NF-κB is constitutively activated, was used in this study.MethodsExpression of p65 protein in fractionated KU-19-19 cells was determined by Western blotting analysis. DNA-binding activity of NF-κB was detected by electrophoretic mobility shift assay. The cytotoxic effects and induction of apoptosis by DHMEQ were analyzed, and cytokines in the supernatant of KU-19-19 cells cultured with or without DHMEQ were measured by enzyme-linked immunosorbent assay (ELISA). Athymic nude mice bearing KU-19-19 subcutaneous tumors were subjected to intraperitoneal administration of 2 mg/kg/d DHMEQ for 3 weeks. Tumor growth was monitored and microvessel density, vascular endothelial growth factor expression, and the apoptotic index of tumors were evaluated by tissue immunohistochemistry.ResultsNF-κB was constitutively activated in KU-19-19 cells. DHMEQ reversibly inhibited the DNA-binding activity of NF-κB by blocking its nuclear translocation. Both cell viability and production of cytokines were significantly and dose-dependently suppressed by DHMEQ, and significant apoptosis was also induced. In in vivo studies, the mean tumor volume in mice treated with DHMEQ was significantly smaller than in controls. Immunohistochemical analysis of tumors revealed marked reduction in microvessel density, vascular endothelial growth factor expression, and induction of apoptosis.ConclusionsBlockade of NF-κB function by DHMEQ may be a useful new molecular targeting treatment for highly aggressive bladder cancer.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Urology - Volume 75, Issue 4, April 2010, Pages 805–812
نویسندگان
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