RESUMO
BACKGROUND: We have previously found that Wnt signaling is activated in mesothelioma cells. To clarify the effect of blocking Wnt signaling in mesothelioma, the expression of dishevelled (Dvl), an intermediator of Wnt signaling, was down-regulated by a reformed type of small interfering RNA (siRNA), stealth RNAi, which can reduce the cytotoxic interferon response unlike conventional siRNA. MATERIALS AND METHODS: Mesothelioma cell lines were transfected with stealth RNAi of Dvl, and cell growth and colony formation were examined. The synergistic effect on cell growth of Dvl stealth RNAi and cisplatin in combination was evaluated. RESULTS: Dvl stealth RNAi down-regulated the expression of Dvl-3 in mesothelioma cells and induced cell cycle aberration which caused suppression of cell growth. Colony formation was also suppressed. Dvl stealth RNAi and cisplatin in combination suppressed cell growth synergistically. CONCLUSION: Our data suggest that inhibition of Wnt signaling leads to significant antitumor effects.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Cisplatino/farmacologia , Mesotelioma/tratamento farmacológico , Mesotelioma/genética , Fosfoproteínas/genética , Proteínas Wnt/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Processos de Crescimento Celular , Terapia Combinada , Proteínas Desgrenhadas , Regulação para Baixo , Humanos , Mesotelioma/metabolismo , Mesotelioma/patologia , Fosfoproteínas/biossíntese , Fosfoproteínas/metabolismo , RNA Interferente Pequeno/genética , Transdução de SinaisRESUMO
BACKGROUND: Haemodialysis therapy does not provide renal tubule function, such as active fluid and solute transport, nor metabolic or endocrine action. Moreover, this treatment is usually associated with serious complications and high mortality. We constructed a bioartificial renal tubule device by using renal tubule epithelial cells in an artificial membrane, and evaluated transport properties of the device for 2 weeks. METHODS: A renal epithelial cell line, LLC-PK(1) (Lewis-lung cancer porcine kidney), was seeded on polysulfone hollow fibres in small and large modules. We studied perfusion and leakage of urea nitrogen (UN) and creatinine (Cr), as well as reabsorption of water, glucose and sodium for a period of 2 weeks. RESULTS: Cell-lined hollow fibre membranes significantly reduced the leakage of UN and Cr throughout the 2 week period. Reabsorption of water, glucose and sodium were adequate from days 3 to 10 and gradually decreased thereafter. LLC-PK(1) cells actively transported these substances. Scanning electron microscopy revealed that cells in the hollow fibres on day 8 became completely confluent. However, they became multi-layered and almost obstructed the hollow fibres on day 13. CONCLUSIONS: This bioartificial renal tubule device functioned to reabsorb water, glucose and sodium for approximately 10 days. This is the first report of successful long-term evaluation of a bioartificial renal tubule device. This device, in combination with continuous haemofiltration, may provide treatment to prevent complications of dialysis and raise the quality of life in chronic renal failure patients.