RESUMEN
OBJECTIVES: Nuclear factor κB (NF-κB) is a superfamily of transcription factors that plays a key role in cancer genesis and progression. The present study aimed to examine the expression of NF-κB/p65 in breast cancer and its relationship with prognostic markers such as tumour grade, tumour size, hormone receptors, and HER-2. METHODS: Ninety-nine unselected formalin-fixed paraffin-embedded invasive ductal and lobular tissue sections were evaluated by immunohistochemistry methods to measure the expression of NF-κB/p65, oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2), and Ki-67. We assessed the correlation between NF-κB/p65 and clinicopathological parameters. RESULTS: NF-κB/p65 was found only in the cytoplasm and positively correlated with large tumours (≥2 cm) and high-grade tumours (p < 0.001 and p = 0.018, respectively). Other breast cancer markers, such as histological type (p = 0.766), HER-2 (p = 0.416), PR (p = 0.356), and ER (p = 0.606), had no significant link with the expression of NF-κB/p65. Furthermore, no significant relation with the Ki-67 marker was detected (p = 0.117). CONCLUSIONS: The current study is indicative of a link between overexpression of NF-κB/p65 and both large tumour size and higher grade. This suggests that the expression of NF-κB/p65 is associated with aggressive biological activity in breast cancer; elucidating the mechanisms that lead to NF-κB/p65 cytoplasmic accumulation could lead to the development of novel therapeutic methods.
Asunto(s)
Neoplasias de la Mama , FN-kappa B , Humanos , Femenino , FN-kappa B/metabolismo , Neoplasias de la Mama/patología , Antígeno Ki-67 , Relevancia Clínica , InmunohistoquímicaRESUMEN
BACKGROUND: Camel urine (CU) has been used as traditional treatment in the Arabian Peninsula for centuries. Although, researchers have reported CU anti-cancer effects, the exact mechanism(s) of action involved has not been fully elucidated. The epithelial-mesenchymal transition EMT is a phenotypic switch that promotes the acquisition of a fibroblastoid-like morphology by epithelial tumor cells, resulting in enhanced tumor cell motility and invasiveness. EMT has been shown to contribute to metastasis and chemoresistance of carcinomas. For that, in the present study, we have assessed the potential mechanism (s) by which CU exert its anti-cancer effects and its possible synergistic therapeutic effect with Doxorubicin (DOX) in breast cancer cells. METHODS: Determination of anti-proliferative and apoptosis validation of CU was performed by 3-(4,5-Dimethylthiazol-2-yl)-2,5,-diphenyltetrazolium bromide (MTT), annexin-V-fluorescein isothiocyanate assays, and Western blot. EMT protein markers, migration and invasion of cells were determined by Western blot or immunofluorescent staining, Scratch assay, Transwell invasion assay, respectively. RESULTS: CU applied a significant anti-cancer effect on breast cancer cells via induction of DNA damage and apoptosis in a concentration- and time-dependent manner. Also, CU remarkably reversed the EMT by downregulating N-cadherin and Vimentin expression and upregulating E-cadherin expression. As a result, the stemness, migration and invasion of breast cancer cells were also inhibited, which was likely mediated by NF-κB-Snail signalling pathway and its downstream inflammatory effectors. CU successfully enhanced DOX cytotoxicity by reversing EMT which possibly through inhibition of NF-κB-Snail signalling and subsequently inflammation. Thus, our study provides new mechanistic bases for the therapeutic application of CU that may improve the outcomes of anti-cancer chemotherapy.