RESUMO
Colorectal cancer (CRC) is the third most commonly diagnosed cancer. Celastrol exhibits anti-tumor activities in a variety of cancers. However, the effect of Celastrol on human CRC and the underlying mechanisms still need to be elucidated. The present study aimed to use in vitro and in vivo methods to clarify the anti-tumor effect of Celastrol and use protein microarrays to explore its mechanisms. We demonstrated that Celastrol effectively inhibited SW480 CRC cell proliferation. Two weeks of Celastrol gavage significantly inhibited the growth of xenografts in nude mice. A total of 69 candidate proteins were identified in the protein microarray experiment, including the most highly enriched protein Shoc2, which is a scaffold protein that modulates cell motility and metastasis through the ERK pathway. Celastrol significantly inhibited ERK1/2 phosphorylation in cell lines and xenograft tumors. Down-regulation of Shoc2 expression using Shoc2 siRNA also inhibited ERK1/2 phosphorylation. Furthermore, down-regulation of Shoc2 expression also significantly inhibited proliferation, colony formation, and migration functions of tumor cells. In addition, the LD0 of Celastrol by gavage is equal or more than 80 mg/kg in C57 male mice. In summary, we unraveled the anti-CRC function of Celastrol and confirmed for the first time that it inhibited the ERK1/2 pathway through binding to Shoc2.
Assuntos
Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Peptídeos e Proteínas de Sinalização Intracelular/genética , Triterpenos/administração & dosagem , Animais , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Triterpenos Pentacíclicos , Análise Serial de Proteínas , Ligação Proteica/genética , RNA Interferente Pequeno/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Objective To investigate the application of electronic bronchoscopy in diagnosis of recurrent tracheoe-sophageal fistula of type Ⅲ esophageal atresia. Methods 5 patients were reviewed who were suspected postopera-tive tracheoesophageal fistula recurrence of type Ⅲ esophageal atresia and examined through electronic bron-choscopy combined with injecting Methylene blue into stomach tube from Jan 2010 to Aug 2014. Male to female ra-tio was 4:1. The age was 2~15 months, median age was 7.4 months. Results The 5 cases were found trachea mem-brane fistula by electronic bronchoscope, recurrent tracheoesophageal fistula was diagnosed with Methylene blue in-jected into stomach tube and overflowed from trachea membrane fistula. Examination time is 3~7 minutes, the aver-age is 4.2 minutes. The 5 cases were confirmed by operation. Conclusion Electronic bronchoscopy combined with injecting Methylene blue into stomach tube to diagnose recurrent tracheoesophageal fistula is safe and feasible, the time is short and the diagnosis rate is high.
RESUMO
The cholinergic anti-inflammatory pathway (CAP) is a new neurophysiologic mechanism regulating the immune system, with alpha7 nicotinic acetylcholine receptor (α7nAChR) being its potential pharmacological target. Cumulative studies have demonstrated that activation of α7nAChR can inhibit inflammation through modulating pro-inflammatory cytokines. The role of α7nAChR has been confirmed in a series of inflammatory diseases. This review is aimed to provide new insights for using a7nAChR against inflammatory diseases.
