RESUMO
Numblike (Numbl), a conserved homolog of Drosophila Numb, has been proved to be implicated in early development of the nervous system. A recent study also showed that Numbl played an important role in tumorigenesis and invasion by suppressing NF-κB activation. However, the biological role of Numbl remains unknown in lung cancer up to now. To address the expression of Numbl in the lung cancer cell, four lung cancer cell lines (metastatic cell lines NCI-H292, 95-D, and non-metastatic cell lines A549, HCC827) and non-cancerous human bronchial epithelial cells were used to detect the protein expression of Numbl by western blotting. The results in this study indicated that the expression of Numbl was downregulated in human lung cancer cell lines, especially in metastatic cell lines. To investigate the role of Numbl in lung cancer cell proliferation, apoptosis, and invasion, we generated human lung cancer 95-D cell lines in which Numbl was either overexpressed or depleted. Subsequently, the effects of Numbl on the cell viability, cycle, apoptosis, and invasion properties in 95-D cells were determined with MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] assay, flow cytometry analysis, and Transwell invasion assays. The results indicated that Numbl could decrease cell viability, suppress cell proliferation and invasion, and promote cell apoptosis. In addition, we investigated the effects of Numbl on the expression of the following proteins: TRAF6 (tumor necrosis factor receptor-associated factor 6), p-p65 (phosphor-NF-κB), cyclin D1, caspase-3, and matrix metalloproteinase 9 (MMP9). Results showed that Numbl could decrease the expression of TRAF6, p-p65, cyclin D1, and MMP9 and increase the expression of caspase-3. All these results suggested that Numbl might be involved in the inhibition of growth, proliferation, and invasion of 95-D cells, as well as the potentiation of apoptosis of 95-D cells by abrogating TRAF6-induced activation of NF-κB.
Assuntos
Apoptose , Movimento Celular , Proliferação de Células , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Caspase 3/genética , Caspase 3/metabolismo , Ciclo Celular , Sobrevivência Celular , Ciclina D1/genética , Ciclina D1/metabolismo , Regulação para Baixo , Expressão Gênica , Humanos , Neoplasias Pulmonares , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Invasividade Neoplásica , Fator 6 Associado a Receptor de TNF/genética , Fator 6 Associado a Receptor de TNF/metabolismo , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismoRESUMO
<p><b>OBJECTIVE</b>To assess the effects of tumor necrosis factor-α (TNF-α) in enhancing the radiosensitivity of lung cancer cells in vitro.</p><p><b>METHODS</b>A549 cells were exposed to γ-ray with or without TNF-α treatment. MTT assay was used to evaluate the cell viability, and flow cytometry was performed to assess the cell apoptosis. Western blotting was used to observe the expression of caspase-3 protein in the exposed cells.</p><p><b>RESULTS</b>Compared with the exposed cells without TNF-α treatment, the cells treated with TNF-α showed significantly suppressed cell proliferation, increased the cell apoptosis, altered cell cycle, and increased caspase-3 protein expression after γ-ray exposure.</p><p><b>CONCLUSION</b>TNF-α can enhance the radiosensitivity of A549 cells to increase the efficiency of radiotherapy with γ-ray irradiation.</p>
Assuntos
Humanos , Apoptose , Efeitos da Radiação , Ciclo Celular , Efeitos da Radiação , Linhagem Celular Tumoral , Raios gama , Neoplasias Pulmonares , Tolerância a Radiação , Fator de Necrose Tumoral alfa , FarmacologiaRESUMO
Objective To analyze the expression of molecular biological markers in patients with early stage adenocarcinoma of lung and to determine the correlation between combined expression and prognosis. Methods Pathologic specimens were collected from 68 patients of early stage adenocarcinoma of lung in our hospital between 2000 to 2002. A panel of molecular markers, including Ki-67, Her-2, P16, P53, VEGF, MMP-9 and CD44v6, were chosen for immunohistochemical analysis of the tumor. Cox proportional hazards regression analysis was used to ana-lyze the relationship between expression of these factors and prognosis. Results Muhivariable analysis demonstrated significantly elevated risk for the following molecular markers: P53 (RR=3.228,95.0% CI 1.331-7.828, P=0.010),MMP-9(RR=2.071,95.0% CI 1.062-4.036,P=0.033),VEGF (RR=2.577,95.0% CI 1.124-5.908, P=0.025). The survival period in the patients with combined expression was remarkably shortened. Conclusions Combined evaluation of P53, VEGF and MMP-9 has clinical significance to the prognosis of early stage adenocarcino-ma of lung.
RESUMO
Objective: To assess the peculiarity in fluorine-18 fluorodeoxyglucose (FDG) uptake in patients with bronchial alveolar carcinoma. Methods: From December, 1998 to April, 2002, 22 patients with bronchial alveolar carcinoma (BAC) were imaged with FDG-PET (positron emission tomography) before surgery. Their maximum and mean standard uptake value (SUVmax and SUVmean ) of tumor and SUV of normal lung (SUVlung) were measured. Results: All tumors were detected by FDG-PET. FDG uptake of tumor was higher than that of normal lung (P
