RESUMO
OBJECTIVE: To study the mechanism of the inhibitory effect of ginsenoside Rg3 on colon cancer cell migration. METHODS: Transwell migration assays were performed to investigate the inhibitory effect of ginsenoside Rg3 on SW480 cell migration. Electrophoretic mobility shift assays (EMSAs) and dual luciferase reporter assays were used to study the suppression capability of Rg3 on nuclear factor kappa B (NF-κB) activity. Western blotting was adopted to determine protein levels. RESULTS: Two-hundred micromolar ginsenoside Rg3 significantly inhibited SW480 cell migration (P < 0.05). EMSA showed that Rg3 suppressed the DNA binding ability of NF-κB. Dual luciferase reporter assay showed that Rg3 decreased NF-κB-regulated gene transcription (P < 0.01). Western blots indicated that Rg3 down-regulated expression of the NF-κB-regulated matrix metalloproteinase 9, cyclooxygenase-2 and C-Myc. An NF-κB inhibitor, pyrrolidine dithiocarbamate, enhanced the inhibitory effect of Rg3 on SW480 cell migration. CONCLUSION: Ginsenoside Rg3 has a strong antitumor migration capability by suppressing NF-κB activity and expression of NF-κB-regulated gene products. It could be a good adjuvant for colon cancer patients during the course of chemotherapy.
Assuntos
Neoplasias do Colo/genética , Neoplasias do Colo/fisiopatologia , Ginsenosídeos/farmacologia , NF-kappa B/genética , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Regulação para Baixo/efeitos dos fármacos , Humanos , NF-kappa B/metabolismoRESUMO
BACKGROUND: MUC2 and MUC5AC overproduction is considered to be associated with hepatolithiasis and related to inflammation. However, mechanisms underlying MUC upregulation under inflammatory stimulation in human intrahepatic biliary epithelial cells (HIBECs) are not completely understood. MATERIAL AND METHODS: Expression of MUC2 and MUC5AC mRNA in HIBECs was detected by real-time PCR. Expression of COX-2, EP4, and phosphorylated ERK, JNK and p38MAPK protein was detected by Western blot. Concentrations of PGE2, IL-1ß and TNF-α in cell culture supernatants were measured using the Quantikine Elisa kit. RESULTS: COX-2 expression as well as PGE2 production in HIBECs was upregulated significantly by LPS, which was completely blocked by either TLR4 antagonist or NFκB inhibitor. Selective COX-2 inhibitor suppressed LPS-induced MUC2 and MUC5AC mRNA expression remarkably. Exogenous PGE2 increased MUC2 and MUC5AC mRNA expression in a dosage-dependent manner independent of IL-1ß and TNF-α. PGE2 receptor EP4 agonist elevated MUC2 and MUC5AC expression, whereas EP4 antagonist had the opposite effect. Expression of phosphorylated p38MAPK was upregulated by exogenous PGE2, and p38MAPK inhibitor reduced MUC2 and MUC5AC expression in HIBECs. In addition, it was found that levels of PGE2, MUC2 and MUC5AC in bile samples from the hepatic ducts affected by intrahepatic stones were significantly higher than those from the unaffected hepatic ducts of patients with hepatolithiasis. CONCLUSIONS: Our findings indicate that PGE2 induces MUC2 and MUC5AC expression in HIBECs via EP4-p38MAPK signaling.
Assuntos
Ductos Biliares/efeitos dos fármacos , Dinoprostona/farmacologia , Células Epiteliais/efeitos dos fármacos , Mucina-5AC/metabolismo , Mucina-2/metabolismo , Receptores de Prostaglandina E Subtipo EP4/agonistas , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Bile/metabolismo , Ductos Biliares/enzimologia , Ductos Biliares/imunologia , Western Blotting , Células Cultivadas , Colelitíase/metabolismo , Colelitíase/patologia , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/farmacologia , Dinoprostona/metabolismo , Relação Dose-Resposta a Droga , Ativação Enzimática , Ensaio de Imunoadsorção Enzimática , Células Epiteliais/enzimologia , Células Epiteliais/imunologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-1beta/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Lipopolissacarídeos/farmacologia , Mucina-5AC/genética , Mucina-2/genética , NF-kappa B/metabolismo , Fosforilação , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Prostaglandina E Subtipo EP4/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Regulação para CimaRESUMO
Objective To discuss the diagnostic value of DSA for massive hemorrhage in lower gastrointestinal tract resulting from tumour. Methods 24 patients with massive lower gastrointestinal hemorrhage were performed DSA and then operated as tumour. Results Among 24 patients, 17 cases demonstrated direct signs of hemorrhage, 9 cases visible turnout vessels; 24 patients all showed clumping tumour-specifie dyeing. Conclusion DSA is of great value to determining the location and qualitation of the massive lower gastrointestinal hemorrhage resuhing from tumours.
