کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4302540 1288458 2011 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Targeting the JNK Signaling Pathway Potentiates the Antiproliferative Efficacy of Rapamycin in LS174T Colon Cancer Cells
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی عمل جراحی
پیش نمایش صفحه اول مقاله
Targeting the JNK Signaling Pathway Potentiates the Antiproliferative Efficacy of Rapamycin in LS174T Colon Cancer Cells
چکیده انگلیسی

BackgroundTargeting the mTOR signaling pathway with rapamycin in cancer therapy has been less successful than expected due in part to the removal of a negative feedback loop resulting in the over-activation of the PI3K/Akt signaling pathway. As the c-Jun N-terminal kinase (JNK) signaling pathway has been found to be a functional target of PI3K, we investigate the role of JNK in the anticancer efficacy of rapamycin.Materials and MethodsThe colon cancer cell line LS174T was treated with rapamycin and JNK phosphorylation was analyzed by Western Blot. Overexpression of a constitutively negative mutant of JNK in LS174T cells or treatment of LS174T cells with the JNK inhibitor SP600125 were used to determine the role of JNK in rapamycin-mediated tumor growth inhibition.ResultsTreatment of LS174T cells with rapamycin resulted in the phosphorylation of JNK as observed by Western Blot. The expression of a negative mutant of JNK in LS174T cells or treatment of LS174T cells with SP600125 enhanced the antiproliferative effects of rapamycin. In addition, in vivo, the antitumor activity of rapamycin was potentiated on LS174T tumor xenografts that expressed the dominant negative mutant of JNK.ConclusionsTaken together, these results show that rapamycin-induced JNK phosphorylation and activation reduces the antitumor efficacy of rapamycin in LS174T cells.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Surgical Research - Volume 167, Issue 2, 15 May 2011, Pages e193–e198
نویسندگان
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