RESUMEN
BACKGROUND: Bromodomain-containing protein 4 (BRD4) inhibition is a new therapeutic strategy for many malignancies. In this study, we aimed to explore the effect of BRD4 inhibition by JQ1 on in vitro cell growth, migration and invasion of salivary adenoid cystic carcinoma (SACC). METHODS: The human normal epithelial cells and SACC cells (ACC-LM and ACC-83) were treated with JQ1 at concentrations of 0, 0.1, 0.5 or 1 µM. Cell Counting Kit-8 (CCK-8) assay was performed to evaluate cell proliferation. Cell apoptosis and cell cycle distribution was evaluated by Flow cytometry. Immunofluorescence staining was used to examine the expression of BRD4 in SACC cells. The quantitative real-time polymerase chain reaction (qRT-PCR) assay and western blot assay were performed to examine messenger RNA (mRNA) and protein levels in SACC cells. Wound- healing assay and transwell assay were used to evaluate the activities of migration and invasion of SACC cells. RESULTS: JQ1 exhibits no adverse effects on proliferation, cell cycle and cell apoptosis of the normal human epithelial cells, while suppressed proliferation and cell cycle, and induced apoptosis of SACC cells, down-regulated the mRNA and protein levels of BRD4 in SACC cells, meanwhile reduced protein expressions of c-myc and BCL-2, two known target genes of BRD4. Moreover, JQ1 inhibited SACC cell migration and invasion by regulating key epithelial-mesenchymal transition (EMT) characteristics including E-cadherin, Vimentin and Twist. CONCLUSIONS: BRD4 is an important transcription factor in SACC and BRD4 inhibition by JQ1 may be a new strategy for SACC treatment.
Asunto(s)
Humanos , Azepinas/farmacología , Factores de Transcripción/antagonistas & inhibidores , Triazoles/farmacología , Neoplasias de las Glándulas Salivales/tratamiento farmacológico , Proteínas Nucleares/antagonistas & inhibidores , Movimiento Celular/efectos de los fármacos , Carcinoma Adenoide Quístico/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Invasividad Neoplásica/patología , Neoplasias de las Glándulas Salivales/patología , Regulación hacia Abajo , Carcinoma Adenoide Quístico/patología , Proteínas de Ciclo Celular , Línea Celular Tumoral , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
El carcinoma adenoide quístico representa aproximadamente un 25 por ciento de los tumores de cabeza y cuello, ubicado principalmente a nivel de paladar, labio y mucosa bucal. Mantiene un curso lento pero con probabilidad de metástasis a largo plazo con diseminación de predominio vascular y raramente a nódulos linfáticos. Clínicamente se manifiesta como indolente manifestado principalmente como una masa. El método diagnóstico más importante es el examen físico con exámenes complementarios por medio de ultrasonido y dependiendo de características propias de la masa se solicitar resonancia magnética para delimitar patología como guía durante procedimiento quirúrgico. Como tratamiento de primera línea se utiliza la resección quirúrgica y se ha demostrado mejores resultados con la agregación de radioterapia.
Asunto(s)
Humanos , Carcinoma Adenoide Quístico/cirugía , Carcinoma Adenoide Quístico/diagnóstico , Carcinoma Adenoide Quístico/fisiopatología , Carcinoma Adenoide Quístico/tratamiento farmacológico , Carcinoma Adenoide Quístico/radioterapiaRESUMEN
Adenoid cystic carcinoma (ACC) of the lacrimal gland is a rare tumor from the epithelial structure. It is rare in children. The authors report a case of ACC in a girl child. Extensive excision of the tumor is advised to prevent later recurrences. Local control can be better achieved by a combination of radiochemotherapy as ACC has been shown to recur event after 10 years.