RESUMO
This study is to investigate the effect of curcumin on the induction of glutathione S-transferases (GST) and NADP(H):quinone oxidoreductase (NQO) and explore their possible molecular mechanism. The activity of GST, NQO and cellular reduced glutathione (GSH) content were measured by spectrophotometrical methods. Cellular changes in the distribution of NF-E2 related factor 2 (Nrf2) were detected by Western blotting analysis. Nrf2-AREs (antioxidant-responsive elements) binding activity was examined by electrophoretic mobility shift assay (EMSA). Treatment of HT-29 human colon adenocarcinoma cells with curcumin dramatically induced the activity of GST and NQO at the range of 10-30 micromol x L(-1). Curcumin exposure caused a significant increase in cellular GSH content rapidly as early as 3 h. Moreover, curcumin triggered the accumulation of Nrf2 in nucleus, and increased Nrf2 content in ARE complexes. These results demonstrated that induction of GST and NQO activity by curcumin may be mediated by translocation of transcription factor Nrf2 from cytoplasm to nuclear and increased binding activity of Nrf2-ARE complexes.
Assuntos
Humanos , Antineoplásicos , Farmacologia , Antioxidantes , Metabolismo , Núcleo Celular , Metabolismo , Curcumina , Farmacologia , Indução Enzimática , Glutationa , Metabolismo , Glutationa Transferase , Metabolismo , Células HT29 , NAD(P)H Desidrogenase (Quinona) , Metabolismo , Fator 2 Relacionado a NF-E2 , Metabolismo , Elementos de Resposta , Transdução de SinaisRESUMO
Objective To explore a more reasonable and effective therapeutic regimen and evaluate prognostic factors in hepatoblastoma patients after combined therapy.Methods Sixteen patients diagnosed on hepatoblastoma between Jan.2000 and Nov.2007 were reviewed and followed-up.Resection with chemotherapy was taken among 16 cases.Chemotherapy included pre-operation and post-operation.Five cases were cured by transcatheter arterial chemombolization(TACE).Six cases were cured by single chemotherapy(both TACE and single chemotherapy were taken in 2 cases).Five cases weren't cured by pre-operation chemotherapy.Nine cases were subjected to curative resection,3 cases to alleviative resection,2 cases with single chemotherapy,1 case with single TACE,and 1 case refused operation and left hospital.Their mean survival duration was 13.5 months(3-98 months).SPSS 13.0 software was used to analyze the data.Results The total survival rate of cases as stage Ⅳ as lower than cases as stage Ⅰ,Ⅱand Ⅲ.Both alpha-fetoprotein(AFP)100 000 ?g/L cases had worse survival rate.The prognosis of mixed type was better than fetal type,embryonal type and anaplasia type.The survival rate of cases with standard chemotherapy was higher than cases with unstandard chemotherapy.And the surgical resection cases had better survival chance than non-surgical resection cases.The survival rate of surgical residual cases was worse than non-surgical residual cases.Conclusions Chemotherapy can improve the total survival rate and long-term survival rate of hepatoblastoma patients.TACE is a safe and effective choice for hepatoblastoma patients.We need to be alert and make the diagnosis as early as possibe,and treat it early and properly.