Abstract：OBJECTIVE To investigate the effect and related mechanism of chrysin on the invasion and metastasis of human colon cancer HCT-116 cells in vitro and in vivo. METHODS CCK-8 was used to detect the inhibitory effect of chrysin on the proliferation of HCT-116 cells. The effects of chrysin on cell migration and invasion were detected by scratch and Transwell. Western blot was used to detect the effects of chrysin on the expression levels of EMT-related proteins E-cadherin, N-cadherin, Vimentin, and Snail in HCT-116 cells and the effect of chrysin on the expression of YAP protein in HCT-116 cells. SiRNA interference assay was used to investigate the effect of YAP low expression on chrysin in HCT-116 cell invasion and EMT process. Experimental lung metastasis model was constructed to investigate the effect of chrysin on the metastasis of HCT-116 cells in vivo. RESULTS Chrysin could significantly inhibit the proliferation of HCT-116 cells at concentration higher than 8 μmol·L-1, and had no significant cytotoxicity on HCT-116 cells when the concentration was below 8 μmol·L-1. Chrysin of 1, 2 and 4 μmol·L-1 inhibited the migration and invasion of HCT-116 cells in a dosage-dependent manner. Western blot results showed that chrysin could up-regulate the protein expression of E-cadherin and down-regulate the protein expression of N-cadherin, Vimentin, and the transcription factor Snail. It was also found that chrysin could down-regulate the protein level of YAP, while down-regulation of YAP could significantly reverse the inhibition of chrysin on migration and invasion of HCT-116 cells and the promotion effect of chrysin on the EMT process of HCT-116 cells by siRNA. The lung metastasis experiments showed that chrysin significantly inhibited the pulmonary metastasis nodules of HCT-116 cells. CONCLUSION This study shows that chrysin can inhibit the invasion and metastasis of HCT-116 cells in vitro and in vivo, and the mechanism is related to the inhibition of YAP and down-regulation of EMT.
张雯, 刘赟心, 万盟, 朱余兵. 白杨素调控YAP介导的EMT进程抑制人结肠癌HCT-116细胞转移的机制研究[J]. 中国药学杂志, 2020, 55(23): 1948-1954.
ZHANG Wen, LIU Yun-xin, WAN Meng, ZHU Yu-bing. The Inhibition Mechanism of Chrysin on the Metastasis of Human Colon Cancer HCT-116 Cells by Regulating YAP-Mediated EMT Process. Chinese Pharmaceutical Journal, 2020, 55(23): 1948-1954.
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