RESUMEN
Previous literatures reported insulin-like growth factor-2 messenger RNA-binding protein 3 (IGF2BP3) is a poor prognostic marker for colorectal cancer (CRC) patients. However, basic research on the effect and biological role of IGF2BP3 in CRC was still scare. Real-time quantitative polymerase chain reaction and western blot analysis were used to examine IGF2BP3 expression level in tumors and paired normal tissues from CRC patients. Tissue microarrays with 192 CRC patients were subjected to immunohistochemical staining to analyze the prognostic value of IGF2BP3. Proliferation assays, migration assays, and xenograft tumor formation in nude mice were performed to assess the biological role of IGF2BP3 in CRC cells. IGF2BP3 expression was significantly upregulated in tumor tissues compared with the matched normal tissues both in messenger RNA and protein level and was associated with worse prognosis. IGF2BP3 knockdown made cell cycle arrest to impair the proliferation ability of CRC cells and further inhibited the xenograft tumor growth in nude mice, also inhibited the migration ability of CRC cells via inducing epithelial-mesenchymal transition. Therefore, the research demonstrated that increased IGF2BP3 expression promoted the aggressive phenotypes of CRC cells. Targeted IGF2BP3 could be a novel and effective gene therapy for CRC patients to make a better prognosis.
Asunto(s)
Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Regulación Neoplásica de la Expresión Génica , Proteínas de Unión al ARN/genética , Anciano , Animales , Puntos de Control del Ciclo Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Supervivencia sin Enfermedad , Transición Epitelial-Mesenquimal/genética , Femenino , Células HEK293 , Humanos , Masculino , Ratones Desnudos , Persona de Mediana Edad , Análisis Multivariante , Fenotipo , Proteínas de Unión al ARN/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Scope: Non-alcoholic steatohepatitis (NASH) is characterized by lipid accumulation in hepatocytes and inflammatory cell infiltration. In view of the anti-oxidative and anti-inflammatory effects of polydatin, the current study aimed to investigate the pharmacological effects of polydatin on NASH and its related fibrosis. Methods: C57BL/6 mice were fed with methionine-choline deficient (MCD) diet to induce NASH and liver fibrosis, and treated with or without polydatin (5 mg/kg, every other day, i.p) for 4 weeks. HepG2 cells induced by palmitic acid (PA) were treated with polydatin. Results: The elevations of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), active caspase-3, TUNEL-positive cells, and triglyceride content were decreased by polydatin treatment. In addition, administration of polydatin to MCD-fed mice reduced oxidative stress by down-regulating NOX4 enzymes. Furthermore, the reduction in inflammation and CD68 macrophage activation correlated with inhibition of toll-like receptor (TLR)-4/NF-κB p65 signaling pathway by polydatin treatment. Polydatin also attenuated lipid accumulation, inflammation and apoptosis in HepG2 cells challenged by palmitic acid (PA) combined with or without lipopolysaccharide (LPS). Finally, the reduction of hepatic fibrosis by polydatin treatment corresponded to a reduction in hepatic gene expression of fibrosis markers. Conclusions: These results suggest that polydatin prevents NASH and fibrosis via inhibition of oxidative stress and inflammation, highlighting polydatin as a potential therapeutic agent for prevention and treatment of NASH.