Reflux composition influences the level of NF-κB activation and upstream kinase preference in oesophageal adenocarcinoma cells.

摘要: Oesophageal adenocarcinoma (OA) incidence is rising and prognosis poor. Understanding the molecular basis of this malignancy key to finding new prevention treatment strategies. Gastroesophageal reflux disease primary cause OA, usually managed with acid suppression therapy. However, often does little control carcinogenic bile reflux. The transcription factor nuclear kappa B (NF-κB) plays a role in pathogenesis OA its activity associated poor response chemotherapy, making it an attractive therapeutic target. We sought decipher different acids NF-κB activation oesophageal cell lines using short, physiologically relevant exposure times. effect acidic or neutral extracellular pH was investigated concurrently, mimic vivo conditions without suppression. found that some activated greater extent when combined acid, whereas others did so absence, at pH. precise composition individual's reflux, coupled whether they are taking suppressants may therefore dictate oesophagus, hence likelihood histological progression chemotherapy success. Regardless pH, kinase inhibitor κB pivotal mediating induced activation. Its importance confirmed further as increased patient samples. identified kinases important signalling cells, which provide suitable targets for intervention.