کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4303590 1288482 2009 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Sulindac Prevents Carcinogen-Induced Intrahepatic Cholangiocarcinoma Formation In Vivo
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی عمل جراحی
پیش نمایش صفحه اول مقاله
Sulindac Prevents Carcinogen-Induced Intrahepatic Cholangiocarcinoma Formation In Vivo
چکیده انگلیسی

BackgroundIntrahepatic cholangiocarcinoma (ICC) incidence and mortality are increasing in the United States and worldwide. ICC etiologies involve chronic inflammation. We hypothesize that the nonsteroidal anti-inflammatory agent sulindac may prevent ICC by targeting cyclooxygenase-1 and -2 (COX-1, -2) as well as COX-independent pathways.Materials and MethodsICC was induced with the carcinogen N-nitrosobis(2-oxopropyl)amine (BOP) in Syrian golden hamsters. Cholangiocarcinogenesis was accelerated by a choline-deficient diet and administration of DL-ethionine and L-methionine. Hamsters were gavaged twice daily for 10 wk with vehicle or sulindac 25, 50, or 75 mg/kg/dose. Harvested livers underwent gross and histopathological examinations. Tissues were analyzed by immunostaining, Western blot, and enzyme-linked immunosorbent assay (ELISA).ResultsICC incidence and multiplicity were decreased in sulindac treatment groups versus control (P < 0.05). In addition, ICC and nontumor lesion sizes decreased in treatment versus control animals. Proliferative indices (Ki-67 immunostaining) decreased and apoptosis (ApopTag immunostaining) increased in treatment versus control (P < 0.05). No changes in COX-1 and -2 protein levels were detected by Western blot. Furthermore, prostaglandin E2 (PGE2) levels were unchanged in treatment and control serum and liver tissues (P > 0.05), suggesting that the antitumor effects of sulindac are mediated by COX-independent mechanisms. Nuclear p65 (activated NF-κB) immunostaining decreased (P < 0.05), and protein levels of the NF-kB inhibitor IκB-α increased in treatment versus control groups. p65 ELISA of liver extracts confirmed decreased NF-κB binding activity in sulindac-treated versus control animals (P < 0.05).ConclusionSulindac effectively prevents experimental cholangiocarcinogenesis, in part by inhibiting the NF-κB pathway.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Surgical Research - Volume 157, Issue 1, November 2009, Pages e87–e95
نویسندگان
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