Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Department of Otolaryngology, Chung Shan Medical University Hospital, Taichung, Taiwan.
Environ Toxicol. 2022 May;37(5):1244-1253. doi: 10.1002/tox.23480. Epub 2022 Feb 3.
Nasopharyngeal carcinoma (NPC) is endemic in Southeast Asia and the main cause of treatment failure is metastasis. A lot of biological and pharmacological actions of dihydromyricetin (DHM) have been reported such as regulating glucose and anti-cancer effects. The effects of DHM on the cancer invasion and migration of NPC, however, are still unclear. We therefore investigated the in vitro anti-metastatic properties of DHM on three human NPC cell lines (HONE-1, NPC-39, and NPC-BM), as well as the underlying signaling pathways. Our study revealed that DHM could suppress the migration and invasion in NPC cells. Gelatin zymography assay and western blotting assays demonstrated that DHM suppressed the enzyme activity and protein expression of matrix metalloproteinases-2 (MMP-2). Mitogen-activated protein kinases were also investigated to elucidate the signaling pathway, which showed that phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) was inhibited after the treatment of DHM. In conclusion, our data revealed that DHM inhibited the migration and invasion of NPC cells by suppressing the expression of MMP-2 via down regulating the ERK1/2 signaling pathway.
鼻咽癌（NPC）在东南亚地区高发，其治疗失败的主要原因是转移。二氢杨梅素（DHM）具有调节葡萄糖和抗癌等多种生物学和药理学作用。然而，DHM 对 NPC 癌症侵袭和迁移的影响尚不清楚。因此，我们研究了 DHM 对三种人 NPC 细胞系（HONE-1、NPC-39 和 NPC-BM）的体外抗转移特性及其潜在的信号通路。我们的研究表明，DHM 可抑制 NPC 细胞的迁移和侵袭。明胶酶谱分析和 Western blot 分析表明，DHM 可抑制基质金属蛋白酶-2（MMP-2）的酶活性和蛋白表达。还研究了丝裂原活化蛋白激酶以阐明信号通路，结果表明 DHM 处理后细胞外信号调节激酶 1 和 2（ERK1/2）的磷酸化受到抑制。综上所述，我们的数据表明，DHM 通过下调 ERK1/2 信号通路抑制 MMP-2 的表达，从而抑制 NPC 细胞的迁移和侵袭。
