کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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4281001 | 1611571 | 2009 | 7 صفحه PDF | دانلود رایگان |
BackgroundCarcinoids are neuroendocrine (NE) tumors with limited treatment options. Raf-1 pathway activation has been shown to suppress hormone production in carcinoid cells. We investigated a novel treatment for carcinoid cell growth based on pharmacologic Raf-1 activation using the compound tautomycin (TTY).MethodsHuman carcinoid cells were treated with TTY for 48 hours. Western blot analysis was used to demonstrate Raf-1 pathway activation by phosphorylation of ERK1/2 and to determine the effect on NE tumor markers. Cellular growth was measured by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay.ResultsTreatment with TTY resulted in dose-dependent activation of the Raf-1 pathway. Furthermore, a significant decrease in NE tumor markers was seen. Importantly, TTY inhibited carcinoid cellular growth and induced the cell-cycle inhibitors p21 and p27.ConclusionTTY activates the Raf-1 pathway, limits carcinoid cell growth, and suppresses NE marker production in vitro. This new compound warrants further investigation in animal models of carcinoid cancer.
Journal: The American Journal of Surgery - Volume 197, Issue 3, March 2009, Pages 313–319