کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2568805 1128485 2013 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Action of hexachlorobenzene on tumor growth and metastasis in different experimental models
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Action of hexachlorobenzene on tumor growth and metastasis in different experimental models
چکیده انگلیسی

Hexachlorobenzene (HCB) is a widespread organochlorine pesticide, considered a possible human carcinogen. It is a dioxin-like compound and a weak ligand of the aryl hydrocarbon receptor (AhR). We have found that HCB activates c-Src/HER1/STAT5b and HER1/ERK1/2 signaling pathways and cell migration, in an AhR-dependent manner in MDA-MB-231 breast cancer cells. The aim of this study was to investigate in vitro the effect of HCB (0.005, 0.05, 0.5, 5 μM) on cell invasion and metalloproteases (MMPs) 2 and 9 activation in MDA-MB-231 cells. Furthermore, we examined in vivo the effect of HCB (0.3, 3, 30 mg/kg b.w.) on tumor growth, MMP2 and MMP9 expression, and metastasis using MDA-MB-231 xenografts and two syngeneic mouse breast cancer models (spontaneous metastasis using C4-HI and lung experimental metastasis using LM3). Our results show that HCB (5 μM) enhances MMP2 expression, as well as cell invasion, through AhR, c-Src/HER1 pathway and MMPs. Moreover, HCB increases MMP9 expression, secretion and activity through a HER1 and AhR-dependent mechanism, in MDA-MB-231 cells. HCB (0.3 and 3 mg/kg b.w.) enhances subcutaneous tumor growth in MDA-MB-231 and C4-HI in vivo models. In vivo, using MDA-MB-231 model, the pesticide (0.3, 3 and 30 mg/kg b.w.) activated c-Src, HER1, STAT5b, and ERK1/2 signaling pathways and increased MMP2 and MMP9 protein levels. Furthermore, we observed that HCB stimulated lung metastasis regardless the tumor hormone-receptor status. Our findings suggest that HCB may be a risk factor for human breast cancer progression.


► HCB enhances MMP2 and MMP9 expression and cell invasion in MDA-MB-231, in vitro.
► HCB-effects are mediated through AhR, HER1 and/or c-Src.
► HCB increases subcutaneous tumor growth in MDA-MB-231 and C4-HI in vivo models.
► HCB activates c-Src/HER1 pathway and increases MMPs levels in MDA-MB-231 tumors.
► HCB stimulates lung metastasis in C4-HI and LM3 in vivo models.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 268, Issue 3, 1 May 2013, Pages 331–342
نویسندگان
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