Investigating Prostaglandin E2 activation of the p38 pathway of oesophageal squamous cell carcinoma

Background, aim and objectives: Oesophageal squamous cell carcinoma (OSCC) is an endemic disease. Epidemiologic studies driven by investigation of Sammon in a region with one of the highest prevalence, linked a predisposition to develop OSCC to a high consumption of maize via reflux disease and chronic oesophagitis. In that context, it was postulated that prostaglandin E2 (PGE2), a hormone derived from a main component of maize, continuously triggers activation of proliferation and inflammation pathways. This work aimed at assessing the role of p38, a mitogen-activated protein kinase (MAPK), in the potential of PGE2 to trigger cellular proliferation, transcription and expression of proliferative (Cyclin D1) and inflammatory (IL-6) mediators in a human epithelial oesophageal cell line (Het1a).
Methods: The proliferation potential of PGE2 via p38 was assessed by MTT assay on Het1a. The effect of H2O2 treatments was also assessed as a positive control. Then, RNA and protein samples were extracted from that cell line previously PGE2-treated. Transcription and expression profiles were studied over time respectively by quantitative polymerase chain reaction (qPCR) and western blot. The role of p38 was assessed by addition of a specific inhibitor, SB203580, to the cells under investigation.
Results and Discussion: It was shown that PGE2 alone could not trigger proliferation of the Het1a cell line. Though, the effect of p38 might be positive. Acute H2O2 treatments turned out encouraging in the development of a model of p38 activation. Regulation of Cyclin D1 and IL-6 transcription was suggested to occur through PGE2 and via the p38 pathway. The Cyclin D1 and IL-6 transcripts were respectively overexpressed and downregulated in a bimodal manner, the second peak relying exclusively on p38 activation. Both observations could be supported by a positive feedback theory involving cyclooxygenase (COX)-2.
Conclusions: Even though PGE2 was shown not to be sufficient to promote Het1a proliferation, regulation of Cyclin D1 and IL-6 transcription via p38 was observed. Furthermore, the expression profile might support the Sammon-Pink theory.