1alpha, 25-dihydroxyvitamin D3 inhibits esophageal squamous cell carcinoma progression by reducing IL-6 signaling
Menée sur des lignées cellulaires de carcinome épidermoïde de l'œsophage et à l'aide de xénogreffes sur un modèle murin, cette étude met en évidence un mécanisme par lequel la 1,25- dihydroxy-vitamine D3 (un métabolite de la vitamine D3) inhibe la progression tumorale en réduisant la signalisation de l'interleukine IL-6
The aim of this study was to highlight the role of 1α, 25-dihydroxyvitamin D3 (calcitriol) in esophageal squamous cell carcinoma (SCC). The human esophageal SCC cell lines CE81T and TE2 were selected for cellular and animal experiments to investigate the changes in tumor behavior after calcitriol supplementation and the underlying mechanisms. Moreover, we evaluated the relationship between calcitriol supplementation, myeloid-derived suppressor cell (MDSC) recruitment, IL-6 levels, and tumor progression by 4-nitroquinoline 1-oxide (4-NQO) -induce esophageal tumor animal model. In this study, we demonstrated that calcitriol supplementation inhibited aggressive tumor behavior both in vitro and in vivo. The underlying changes included increased cell death, a lower degree of epithelial-mesenchymal transition and inhibited IL-6 signaling. In a 4-NQO-induced esophageal tumor animal model, Increased IL-6 and MDSC recruitment linked with invasive esophageal tumors. Supplementation with calcitriol attenuated the level of IL-6, the induction of MDSCs and the incidence of 4-NQO- induced invasive tumors. Moreover, the IL-6 induced changes in C57 mice including augmented MDSC recruitment, increased levels of ROS and p-Stat3 in MDSCs, and higher suppressive function of MDSCs in T cell proliferation, which were abrogated by calcitriol supplementation. Based on our results, we concluded that calcitriol abrogated the IL-6-induced aggressive tumor behavior and MDSC recruitment to inhibit esophageal tumor promotion. Therefore, we suggest that supplementation with vitamin D3 may be a promising strategy for the prevention and treatment of esophageal SCC.
http://mct.aacrjournals.org/content/early/2015/03/28/1535-7163.MCT-14-0952.abstract