期刊
TOXICOLOGY IN VITRO
卷 28, 期 4, 页码 552-561出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2014.01.002
关键词
Destruxin B; EMT; HCC; Metastasis; Sorafenib combination; Wnt/beta-catenin
类别
资金
- National Science Council of Taiwan (NSC) [100-2113-M-324-001-MY3, 101-2811-M-324-001, 101-2325-B-038-005, 100-2313B-038-001-MY3]
- Taipei Medical University [101 TMU-SHH-04, 102 TMU-SHH-02]
The aberrant activation of Wnt/beta-catenin signaling plays an important role in the carcinogenesis and progression of hepatocellular carcinoma (HCC). Therefore, the Wnt/beta-catenin signaling molecules are attractive candidates for the development of targeted therapies for this disease. The present study showed that destruxin B (DB) inhibits the proliferation and induces the apoptosis of HCC cells by decreasing the protein expression of anti-apoptotic Bcl-2 and Bcl-xL and increasing the expression of the proapoptotic protein Bax. More importantly, DB also attenuates Wnt-signaling in HCC cells by downregulating beta-catenin, Tcf4, and beta-catenin/Tcf4 transcriptional activity, which results in the decreased expression of p-catenin target genes, such as cyclin D1, c-myc, and survivin. Furthermore, DB affects the migratory and invasive abilities of Sk-Hep1 cells through the suppression of markers of the epithelial-mesenchymal transition (EMT). A synergistic anti-proliferative and migratory effect was achieved using the combination of DB and sorafenib in Sk-Hep1 cells. In conclusion, DB acts as a novel Wnt/beta-catenin inhibitor and reduces the aggressiveness and invasive potential of HCC by altering the cells' EMT status and mobility. DB in combination with sorafenib may be considered for future clinical use for the management of metastatic HCC. 2014 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据