| Title | The antimetastatic effect and underlying mechanisms of thioredoxin reductase inhibitor ethaselen |
| Authors | Zheng, Xiaoqing Chen, Yifan Bai, Man Liu, Yuxi Xu, Binyuan Sun, Ruoxuan Zeng, Huihui |
| Affiliation | Peking Univ, State Key Lab Nat & Biomimet Drugs, 38 Xueyuan Rd, Beijing 100191, Peoples R China Peking Univ, Sch Pharmaceut Sci, Dept Chem Biol, 38 Xueyuan Rd, Beijing 100191, Peoples R China Purdue Univ, Dept Med Chem & Mol Pharmacol MCMP, Coll Pharm, 575 Stadium Mall Dr, W Lafayette, IN 47907 USA |
| Keywords | Invasion and metastasis Thioredoxin reductase Reactive oxygen species (ROS) Epidermal growth factor receptor (EGFR) Epithelial-mesenchymal transition (EMT) |
| Issue Date | 2019 |
| Publisher | FREE RADICAL BIOLOGY AND MEDICINE |
| Abstract | Treating cancer metastasis is of vital importance to prolong patients' survival. Thioredoxin reductase (TrxR) is overexpressed in many cancer types and has been recognized as an anti-cancer target. The organoselenium compound ethaselen (BBSKE) has been proved to be a TrxR inhibitor and inhibit various types of tumor growth. However, whether BBSKE could inhibit tumor metastasis remains unclear. In this study, we aim to explore the antimetastatic effect of BBSKE and underlying mechanisms. BBSKE was found to dose-dependently suppress migration and invasion of MCF-7 and LoVo cells in vitro. The underlying mechanisms may include inhibition of TrxR activity, elevation of reactive oxygen species (ROS), decrease of EGFR activation and HER2 expression. Besides, the epithelial to mesenchymal transition process and expression of CD44, MMP-9, VEGFR2 and PD-L1 were also abrogated. Decreased migration and invasion, lower expression levels of EGFR, HER2, N-cadherin, CD44, MMP-9, VEGFR2 and PD-L1 were also observed in TrxR1-knockdown MCF-7 and LoVo cells. In the mouse breast cancer 4T1 model, BBSKE not only inhibited progression of primary tumor, but also suppressed formation of metastatic lung nodules and liver micro-metastases, indicating that BBSKE could effectively abolish tumor metastasis. In conclusion, our findings show that BBSKE is able to inhibit migration and invasion of cancer cells in vitro and in vivo, and may be used to prevent and treat metastasis. |
| URI | http://hdl.handle.net/20.500.11897/551238 |
| ISSN | 0891-5849 |
| DOI | 10.1016/j.freeradbiomed.2018.11.030 |
| Indexed | SCI(E) EI |
| Appears in Collections: | 天然药物与仿生药物国家重点实验室 药学院 |
