RESUMEN
Polybrominated diphenyl ethers (PBDEs) are classic and emerging pollutants that are potentially harmful to the human immune system. Research on their immunotoxicity and mechanisms suggests that they play an important role in the resulting pernicious effects of PBDEs. 2,2',4,4'-Tetrabrominated biphenyl ether (BDE-47) is the most biotoxic PBDE congener, and, in this study, we evaluated its toxicity toward RAW264.7 cells of mouse macrophages. The results show that exposure to BDE-47 led to a significant decrease in cell viability and a prominent increase in apoptosis. A decrease in mitochondrial membrane potential (MMP) and an increase in cytochrome C release and caspase cascade activation thus demonstrate that cell apoptosis induced by BDE-47 occurs via the mitochondrial pathway. In addition, BDE-47 inhibits phagocytosis in RAW264.7 cells, changes the related immune factor index, and causes immune function damage. Furthermore, we discovered a significant increase in the level of cellular reactive oxygen species (ROS), and the regulation of genes linked to oxidative stress was also demonstrated using transcriptome sequencing. The degree of apoptosis and immune function impairment caused by BDE-47 could be reversed after treatment with the antioxidant NAC and, conversely, exacerbated by treatment with the ROS-inducer BSO. These findings indicate that oxidative damage caused by BDE-47 is a critical event that leads to mitochondrial apoptosis in RAW264.7 macrophages, ultimately resulting in the suppression of immune function.
Asunto(s)
Éteres Difenilos Halogenados , Mitocondrias , Ratones , Animales , Humanos , Especies Reactivas de Oxígeno/metabolismo , Éteres Difenilos Halogenados/farmacología , Mitocondrias/metabolismo , Macrófagos/metabolismoRESUMEN
OBJECTIVE: To explore the effects and underlying mechanisms of high glucose on in vitro invasiveness of human breast cancer cell line MDA-MB-435. METHODS: The invasiveness of MDA-MB-435 was determined by Matrigel-coated transwell chambers. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were employed to analyze the cellular expression of matrix metalloproteinase-9/matrix metalloproteinase-2/E-cadherin (MMP-9/MMP-2/E-cadherin) gene/protein. RESULTS: The invasive breast cancer cell numbers of each group (Glu 5.5, 11 and 25 mmol/L) were 50 ± 5, 65 ± 6 and 77 ± 3 respectively. Cellular invasion was dramatically enhanced in the Glu 11 and 25 mmol/L group compared with the 5.5 mmol/L group. The MMP-9/MMP-2 protein expression increased significantly in the Glu 11 and 25 mmol/L groups compared with 5.5 mmol/L group while high glucose (Glu 11 and 25 mmol/L group) down-regulated significantly the E-cadherin mRNA/protein expression. CONCLUSION: High glucose can promote the in vitro invasiveness of human breast cancer cells through the altered expression of MMP-9/MMP-2/E-cadherin.
Asunto(s)
Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Glucosa/efectos adversos , Antígenos CD , Cadherinas/metabolismo , Línea Celular Tumoral , Femenino , Humanos , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Invasividad NeoplásicaRESUMEN
BACKGROUND: Cancer stem cells (CSCs) are the cause of cancer recurrence because they are resistant to conventional therapy and contribute to cancer growth and metastasis. Endocrinotherapy is the most common breast cancer therapy and acquired tamoxifen (TAM) resistance is the main reason for endocrinotherapy failure during such therapy. Although acquired resistance to endocrine treatment has been extensively studied, the underlying mechanisms are unclear. We hypothesized that breast CSCs played an important role in TAM-induced resistance during breast cancer therapy. Therefore, we investigated the biological characteristics of TAM-resistant (TAM-R) breast cancer cells. METHODS: Mammosphere formation and tumorigenicity of wild-type (WT) and TAM-R MCF7 cells were tested by a mammosphere assay and mouse tumor xenografts respectively. Stem-cell markers (SOX-2, OCT-4, and CD133) and epithelial-mesenchymal transition (EMT) markers were tested by quantitative real-time (qRT)-PCR. Morphological observation was performed to characterize EMT. RESULTS: After induction of TAM resistance, TAM-R MCF7 cells exhibited increased proliferation in the presence of TAM compared to that of WT MCF7 cells (P < 0.05), indicating enhanced TAM resistance of TAM-R MCF7 cells compared to that of WT MCF7 cells. TAM-R MCF7 cells showed enhanced mammosphere formation and tumorigenicity in nude mice compared to that of WT MCF7 cells (P < 0.01), demonstrating the elevated CSC properties of TAM-R MCF7 cells. Consistently, qRT-PCR revealed that TAM-R MCF7 cells expressed increased mRNA levels of stem cell markers including SOX-2, OCT-4, and CD133, compared to those of WT MCF7 cells (P < 0.05). Morphologically, TAM-R MCF7 cells showed a fibroblastic phenotype, but WT MCF7 cells were epithelial-like. After induction of TAM resistance, qRT-PCR indicated that MCF7 cells expressed increased mRNA levels of Snail, vimentin, and N-cadherin and decreased levels of E-cadherin, which are considered as EMT characteristics (P < 0.05). CONCLUSION: TAM-R MCF7 cells possess CSC characteristics and may be responsible for TAM resistance during breast cancer therapy.
Asunto(s)
Antineoplásicos Hormonales/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Células Madre Neoplásicas/efectos de los fármacos , Tamoxifeno/farmacología , Animales , Neoplasias de la Mama/patología , Resistencia a Antineoplásicos , Transición Epitelial-Mesenquimal , Femenino , Humanos , Células MCF-7 , RatonesRESUMEN
OBJECTIVE: To analyze breast cancer bone metastasis related gene-CXCR4. METHODS: This research screened breast cancer bone metastasis related genes by high-flux gene chip. RESULTS: It was found that the expressions of 396 genes were different including 165 up-regulations and 231 down-regulations. The expression of chemokine receptor CXCR4 was obviously up-regulated in the tissue with breast cancer bone metastasis. Compared with the tissue without bone metastasis, there was significant difference, which indicated that CXCR4 played a vital role in breast cancer bone metastasis. CONCLUSIONS: The bioinformatics analysis of CXCR4 can provide a certain basis for the occurrence and diagnosis of breast cancer bone metastasis, target gene therapy and evaluation of prognosis.
Asunto(s)
Neoplasias Óseas/secundario , Neoplasias de la Mama/genética , Receptores CXCR4/química , Receptores CXCR4/genética , Regulación hacia Arriba , Adulto , Secuencia de Aminoácidos , Neoplasias de la Mama/patología , Biología Computacional , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Persona de Mediana Edad , Datos de Secuencia Molecular , Análisis de Secuencia por Matrices de Oligonucleótidos , Alineación de SecuenciaRESUMEN
BACKGROUND AND AIMS: To investigate the expression of Egfl7 in normal adult human tissues and human epithelial tumors.â© METHODS: RT-PCR and Western blot were employed to detect Egfl7 expression in normal adult human tissues and 10 human epithelial tumors including hepatocellular carcinoma (HCC), lung cancer, breast cancer, prostate cancer, colorectal cancer, gastric cancer, esophageal cancer, malignant glioma, ovarian cancer and renal cancer. Immunohistochemistry and cytoimmunofluorescence were subsequently used to determine the localization of Egfl7 in human epithelial tumor tissues and cell lines. ELISA was also carried out to examine the serum Egfl7 levels in cancer patients. In addition, correlations between Egfl7 expression and clinicopathological features as well as prognosis of HCC and breast cancer were also analyzed on the basis of immunohistochemistry results.â© RESULTS: Egfl7 was differentially expressed in 19 adult human normal tissues and was overexpressed in all 10 human epithelial tumor tissues. The serum Egfl7 level was also significantly elevated in cancer patients. The increased Egfl7 expression in HCC correlated with vein invasion, absence of capsule formation, multiple tumor nodes and poor prognosis. Similarly, upregulation of Egfl7 in breast cancer correlated strongly with TNM stage, lymphatic metastasis, estrogen receptor positivity, Her2 positivity and poor prognosis. â© CONCLUSIONS: Egfl7 is significantly upregulated in human epithelial tumor tissues, suggesting Egfl7 to be a potential biomarker for human epithelial tumors, especially HCC and breast cancer.