RESUMO
The present research focuses on the influence of CCCTC-binding factor (CTCF) on prostate cancer (PC) via the regulation of the FoxO signalling pathway. A bioinformatics analysis was conducted to screen out target genes for CTCF in LNCaP cells and to enrich the relevant pathways in LNCaP cells. It was found that the FoxO pathway was enriched according to the ChIP-seq results of CTCF. The expression of CTCF, pFoxO1a, FoxO1a, pFoxO3a and FoxO3a was tested by RT-qPCR and Western blot. Inhibition of CTCF could lead to the up-regulation of the FoxO signalling pathway. The rates of cell proliferation, cell invasion and apoptosis were examined by MTT assay, cell invasion assay and flow cytometry under different interference conditions. Down-regulation of CTCF could suppress cell proliferation, cell invasion and facilitate cell apoptosis. Lastly, the effect of CTCF on tumour growth was determined in nude mice. Inhibition of CTCF regulated the FoxO signalling pathway, which retarded tumour growth in vivo. In conclusion, CTCF regulates the FoxO signalling pathway to affect the progress of PC.
Assuntos
Fator de Ligação a CCCTC/genética , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O3/genética , Neoplasias da Próstata/genética , Animais , Apoptose/genética , Fator de Ligação a CCCTC/antagonistas & inibidores , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/genética , Xenoenxertos , Humanos , Masculino , Camundongos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Neoplasias da Próstata/patologia , Transdução de Sinais/genética , Ativação Transcricional/genéticaRESUMO
This study was aimed at exploring the underlying mechanisms of ketamine in the SV-40 immortalized human ureteral epithelial (SV-HUC-1) cells. The viability and apoptosis of SV-HUC-1 cells treated with 0.01, 0.1, and 1 mM ketamine were respectively detected via cell counting kit-8 (CCK-8) assay and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining. Reactive oxygen species (ROS) level was measured through ROS probe staining. Apoptosis-related proteins (B-cell lymphoma 2 [Bcl-2] and Bax) and autophagy-associated proteins (light chain 3-I [LC3-I] and LC3-II) were determined by western blot or immunofluorescent assay. Additionally, transmission electron microscopy (TEM) was used to evaluate the formation of autophagosomes. After cotreatment of 3-methyladenine (3-MA) or N-acetyl-l-cysteine (NAC), the biological functions of SV-HUC-1 cells were analyzed to determine the association of ROS with cell viability and autophagy. CCK-8 assay and TUNEL staining indicated that ketamine effectively decreased the viability of SV-HUC-1 cells and accelerated apoptosis of SV-HUC-1 cells through regulating the expression level of IKBα (phospho), nuclear factor кB (P65), Bcl-2, and Bax proteins. Enhanced ROS production was also confirmed in ketamine-treated SV-HUC-1 cells treated with ketamine. Ketamine-induced autophagosomes in SV-HUC-1 cells were observed by means of TEM, and increased levels of LC3 II/I ratio and Beclin 1 were examined through western blot and immunofluorescent assay. Furthermore, ketamine exerted effects on SV-HUC-1 cells in a dose-dependent and time-dependent manner. Additionally, cotreatment of NAC with 3-MA significantly attenuated the ROS level and suppressed the cell autophagy. Ketamine promoted SV-HUC-1 cell autophagy and impaired the cell viability of SV-HUC-1 cells by inducing ROS.
Assuntos
Autofagossomos/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Ketamina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Autofagossomos/metabolismo , Proteína Beclina-1/metabolismo , Linhagem Celular , Humanos , FosforilaçãoRESUMO
RATIONALE: Spontaneous renal rupture is rupture of the renal parenchyma, collecting system, or renal blood vessel, which often occurs in pathological kidney and is clinically less common. Postoperative long-term renal rupture is rarely reported in flexible ureteroscopy treatment of calculus in the upper urinary tract. PATIENT CONCERNS: A 58-year-old man complained of right lower abdominal pain with hematuria for 3âhours after flexible ureteroscopy, combined with holmium laser lithotripsy of right renal calculi was performed 1 month ago. The urinary B-mode ultrasonogram suggested calculi and dilatation at the end of the right ureter, and moderate hydronephrosis of the right kidney. On the second day, the urinary system computed tomography (CT) examination suggested right renal rupture. DIAGNOSIS: Spontaneous rupture of the right renal pelvis. INTERVENTION: The patient underwent conservative treatment after the optimal treatment strategy was reviewed and discussed. OUTCOMES: Urinary system CT re-examination suggested complete absorption of the hematoma and urinary extravasation 3 months later. LESSONS: Calculi obstruction is the most important cause of spontaneous renal rupture. CT is a valuable diagnostic modality, and spontaneous renal rupture should receive tailored treatment.