RESUMO
The gene associated with retinoid-interferon mortality (GRIM-19) has been reported to be correlated with drug resistance, whereas its functional role in prostate cancer (PC) is not fully understood. This study aims to clarify the potential role and molecular mechanisms of GRIM-19 on the response of PC cells to chemical drug docetaxel. mRNA and protein level of GRIM-19 expression in cells and tissues of PC were measured by quantitative real-time PCR and western blot, respectively. Knock-down of GRIM-19 in PC cells was performed using siRNA. Cell apoptosis was determined by flow cytometric analysis. DNA damage in PC cells was detected by γ-H2AX staining. GRIM-19 was downregulated in PC tissues and cell lines. Knock-down of GRIM-19 increased the resistance of PC cells to docetaxel, and overexpression of GRIM-19 promoted docetaxel-induced apoptotic death in PC cells. Mechanistically, GRIM-19 downregulated the expression of the survival gene Rad23b, which promoted DNA damage repair. Overexpression of Rad23b reversed GRIM-19-mediated response to docetaxel in PC cells. GRIM-19 promoted the sensitivity of PC cells to docetaxel by downregulating Rad23b, which may serve as a promising target to develop a better strategy of chemotherapy for PC.
Assuntos
Proteínas Reguladoras de Apoptose/genética , Enzimas Reparadoras do DNA/genética , Proteínas de Ligação a DNA/genética , Docetaxel/uso terapêutico , NADH NADPH Oxirredutases/genética , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Regulação para Cima/genética , Idoso , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/genética , Reparo do DNA/efeitos dos fármacos , Reparo do DNA/genética , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Células PC-3 , Regulação para Cima/efeitos dos fármacosRESUMO
OBJECTIVE: To investigate the distribution of the homeostasis model assessment of insulin resistance (HOMA-IR) among children and adolescent in Zhangzhou city and Zhongshan city. METHODS: Total of 3102 children and adolescent aged 6 to 18-year-old were recruited, which were enrolled in a population-based cross-sectional study. Anthropometric and biochemical parameters were measured. RESULTS: A total of 1528 (49.26%) girls and 1574 (50.74%) boys were included in this study. The concentrations of insulin and fasting glucose gradually increased from 6 to 18 years of age, there was no statistical difference between boys ang girls. The mean values for the BMI were similar in age-matched boys and girls from 6 to 18-year-old ,but for 12 to 15-year-old children was significantly higher in the girls compared with the boys and conversely for 16 to 18-year-old (P < 0.05). The HOMA-IR gradually increased with age and reached a plateau at 12 years of age and there was no markedly differential in gender. CONCLUSION: The glucose levels, insulin concentrations and HOMA-IR exhibited a gradual increase with age. It was suggested that the evaluation of IR in children should be based on percentiles of the HOMA-IR rather than a dichotomous value derived from a single cutoff point.