Abstract
Abstract An epithelial-to-mesenchymal transition (EMT) is one of important phenomenon in tumor metastasis. Oncostatin-M (OSM) belonging to the IL-6 family is a cytokine that participates in invasion and migration of various cancer cells. It is produced by macrophage and stimulates the JAK/STAT signal transduction pathway. In this study, we examined the effect of OSM on EMT of human esophageal carcinoma cells and found a way to inhibit cell metastasis. We first observed morphological changes of tumor cells from an epithelial-like phenotype to a more spindle-shaped, mesenchymal phenotype by OSM. Consistent with these findings, OSM also promoted cell motility using a wound scratch assay and matrigel invasion assay. Moreover, we observed that intracellular stat3 phosphorylation was promoted by the stimulation of OSM by Western blotting. To confirm the contribution of p-stat3, we used a selective JAK2/STAT3 inhibitor cucurbitacin I. As a result, cucurbitacin I strongly inhibited OSM-induced tumor cell invasion and migration. Then, we used two dietary phytochemical resveratrol (polyphenol in grapes) and sulforaphane (isothiocyanate in broccolis), both were reported as candidates of stat3 inhibitor. By the addition of resveratrol or sulforaphane, we found that these markedly inhibited OSM-induced stat3 phosphorylation, the expression of EMT-related genes (snail, slug and vimentin) and tumor cell migration. Overall, our findings provide new evidence that these phytochemicals suppress OSM-induced tumor invasion and migration through inhibiting stat3 phosphorylation and EMT pathway. Citation Format: Eijin Naka, Yuko Takahashi, Hisahiro Matsubara, Kazunori Kato. Inhibitory effect of phytochemicals on oncostatin-M-induced tumor invasion and migration in human esophageal carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5189. doi:10.1158/1538-7445.AM2015-5189
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