کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5917370 1163785 2013 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Cimetidine suppresses lung tumor growth in mice through proapoptosis of myeloid-derived suppressor cells
ترجمه فارسی عنوان
سمیدیدین رشد تومور ریه را در موشها از طریق پروپوپتوز سلولهای سرکوبگر مشتق شده از میلوئید
کلمات کلیدی
سایمتیدین، سلول سرطانی مشتق شده از میلوئید، آپوپتوز تومور ایمنی،
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
چکیده انگلیسی

Cimetidine, a histamine type-2 receptor antagonist, is known to inhibit the growth of several tumors in human and animals, however the mechanism of action underlying this effect remains largely unknown. Here, in the mice model of 3LL lung tumor, cimetidine showed significant inhibition of tumor growth. However, an in vitro study demonstrated that cimetidine showed no effect on proliferation, survival, migration and invasion of 3LL cells. We found that cimetidine reduced CD11b+Gr-1+ myeloid derived-suppressive cell (MDSC) accumulation in spleen, blood and tumor tissue of tumor-bearing mice. In vitro coculture assay showed that cimetidine reversed MDSC-mediated T-cell suppression, and improved IFN-γ production. Further investigation demonstrated that the NO production and arginase I expression of MDSCs were reduced, and MDSCs prone to apoptosis by cimetidine treatment. However, MDSC differentiation was not affect by cimetidine. Importantly, although histamine H2 receptor was expressed in MDSC surface, histamine could not reverse the proapoptosis of cimetidine. Moreover, famotidine also did not have this capacity. We found that cimetidine could induce Fas and FasL expression in MDSC surface, and sequentially regulate caspase-dependent apoptosis pathway. Thus, these findings revealed a novel mechanism for cimetidine to inhibit tumor via modulation of MDSC apoptosis.

Highlights► Cimetidine reduced CD11b+Gr-1+ myeloid derived-suppressive cell (MDSC) accumulation in the mouse model of lung cancer. ► Cimetidine reversed MDSC-mediated T-cell suppression, and improved IFN-γ production. ► MDSCs were prone to apoptosis by cimetidine treatment. ► Cimetidine induced Fas and FasL expression in MDSC surface, and regulated caspase-dependent apoptosis pathway. ► We report a novel mechanism for cimetidine to inhibit tumor via proapoptosis of MDSCs.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Immunology - Volume 54, Issue 1, May 2013, Pages 74-83
نویسندگان
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