Apigenin Inhibits IL-6 Transcription and Suppresses Esophageal Carcinogenesis

作者：Jian-Ge Qiu, Lin Wang, Wenjing Liu, Jufeng Wang, Erjiang Zhao, Feng-Mei Zhou, Xiang-Bo Ji, Lihong Wang, Zhong-Kun Xia, Wei Wang, Marie C.M. Lin, Liu L, Yingxue Huang, Bing‐Hua Jiang · 发表于：Frontiers in Pharmacology · 年份：2019 · DOI：10.3389/fphar.2019.01002 · 被引用次数：45 · 研究领域：Flavonoids in Medical Research、Natural product bioactivities and synthesis、Phytochemistry and Biological Activities

Esophagus cancer is the seventh causes of cancer-related deaths globally. In this study, we analyzed IL-6 gene expression in human esophagus cancer patients, and showed that IL-6 mRNA levels are significantly higher in tumor tissues and negatively correlated with overall survival, suggesting that IL-6 is a potential therapeutic target for esophagus cancer. We further demonstrated that apigenin, a nature flavone product of green plants, inhibited IL-6 transcription and gene expression in human esophagus cancer Eca-109 and Kyse-30 cells. Apigenin significantly and dose-dependently inhibited cell proliferation, and promoted apoptosis while stimulating the cleaved PARP (C-PARP) and Caspase-8 expression. It suppressed VEGF expression, and tumor-induced angiogenesis. Pretreatment of cells with IL-6 could completely reverse apigenin induced cellular changes. Finally, using a preclinical nude mice model subcutaneously xenografted with Eca-109 cells, we demonstrated the in vivo anti-tumor activity and mechanisms of apigenin. Taken together, this study revealed for the first time that apigenin is a new IL-6 transcription inhibitor, and that inhibiting IL-6 transcription is one of the mechanisms by which apigenin exhibits its anti-cancer effects. The potential clinical applications of apigenin in treating esophagus cancer warrant further investigations.