RESUMO
BACKGROUND/AIMS: A major polyphenol of green tea, epigallocatechin-3-gallate (EGCG), has previously been shown to induce cell-cycle arrest and apoptosis in various cancers. However, little is known about its effects on hepatocellular carcinomas (HCCs). METHODS: Four HCC cell lines, HLE, HepG2, HuH-7 and PLC/PRF/5, were treated with EGCG or vehicle. Cell viability was assessed by trypan blue staining and WST-8 assay. Cell-cycle, apoptosis and apoptosis-related proteins in HLE cells were evaluated by flow cytometry and Western blotting. The effect of EGCG was also studied in vivo using a xenograft model. The effect of co-treatment with EGCG and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was also assessed. RESULTS: EGCG inhibited the growth of all HCC cell lines at concentrations of 50-100 microg/ml. In HLE cells, EGCG induced apoptosis but not cell-cycle arrest and appears to have down-regulated Bcl-2alpha and Bcl-xl by inactivation of NF-kappaB. Oral administration of EGCG showed similar effects in HLE xenograft tumors. Co-treatment with EGCG and TRAIL synergistically induced apoptosis in HLE cells. CONCLUSIONS: EGCG induced apoptosis in HLE cells, both in vitro and in vivo. Moreover, it enhanced TRAIL-induced apoptosis. Therefore, EGCG treatment may be useful for improving the prognosis of HCCs.
Assuntos
Anticarcinógenos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Catequina/análogos & derivados , Neoplasias Hepáticas/tratamento farmacológico , Proteína X Associada a bcl-2/metabolismo , Proteína bcl-X/metabolismo , Administração Oral , Animais , Anticarcinógenos/análise , Apoptose , Proteínas Reguladoras de Apoptose/uso terapêutico , Camellia sinensis/química , Carcinoma Hepatocelular/metabolismo , Caspases/metabolismo , Catequina/análise , Catequina/uso terapêutico , Linhagem Celular Tumoral , Regulação para Baixo , Ativação Enzimática , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Glicoproteínas de Membrana/uso terapêutico , Camundongos , Camundongos Endogâmicos , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF , Chá/química , Fator de Necrose Tumoral alfa/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína X Associada a bcl-2/genética , Proteína bcl-X/genéticaRESUMO
We report two patients with gastrointestinal stromal tumors (GISTs) of the small intestine that expressed c-kit protein (CD117). One was a 68-year-old woman with epigastralgia and vomiting. A submucosal tumor of the upper jejunum was detected, and partial resection was carried out. The histology revealed a GIST negative for CD34 but positive for CD117. The other was a 42-year-old woman with progressive anemia, melena and lower abdominal pain. Intussusception was detected, and a partial resection was carried out. A submucosal tumor of the lower jejunum was noted. The histology revealed a GIST positive for both CD34 and CD117.