کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9002311 1118583 2005 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Modulation of 5-fluorouracil cytotoxicity through thymidylate synthase and NF-κB down-regulation and its application on the radiolabelled iododeoxyuridine therapy on human hepatoma cell
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
پیش نمایش صفحه اول مقاله
Modulation of 5-fluorouracil cytotoxicity through thymidylate synthase and NF-κB down-regulation and its application on the radiolabelled iododeoxyuridine therapy on human hepatoma cell
چکیده انگلیسی
The inhibition of thymidylate synthase (TS) by 5-fluorouracil (5-FU) was known to increase the incorporation of radiolabelled iododeoxyuridine (IdUrd) into DNA. The relatively non-toxic compounds such as thiol-containing antioxidant pyrrolidinodithiocarbamte (PDTC) or aromatic fatty acid phenylbutyrate (PB) had been reported to enhance the cytotoxic efficacy of 5-FU. We designed a novel strategy through triplet combination of PB, PDTC and 5-FU to increase the radiolabelled IdUrd uptake and investigated the underlying mechanisms. The growth inhibition and [125I]IdUrd-DNA incorporation by PB, PDTC, 5-FU in different combinations were tested on parent or p21Waf1 transfected Hep3B cells. The combination of PB and PDTC was more effective in enhancing 5-FU cytotoxicity than either drug alone. The combination of PB/PDTC and 5-FU blocked cells in S-phase and resulted in 8.5-fold increase of radiolabelled IdUrd-DNA incorporation. The transfection of p21Waf1 did not change the general pattern of enhancement. Intriguingly, the combination of PB and PDTC effectively down-regulated NF-κB and TS and prevented their up-regulation from 5-FU treatment than either drug alone through a p21Waf1-independent mechanism. Based on this strategy, the 3-drug combination offered potential for improved radiolabelled IdUrd molecular radiotherapy for hepatoma treatment.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 69, Issue 4, 15 February 2005, Pages 617-626
نویسندگان
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