Wang Feng-Jie, Zong Xing-Yu, DU Jun-Long, Wang Wen-Sheng, Yuan De-Pei, Chen Xian-Bing
Minda Hospital of Hubei Minzu University, Enshi 445000.
Medical School of Hubei Minzu University, Enshi 445000.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2019 Sep;35(5):428-432. doi: 10.12047/j.cjap.5809.2019.093.
To investigate the effects of dihydromyricetin (DHM) on the migration and invasion of human gastric cancer MKN45 cells and its mechanism and provide experimental basis for the prevention and treatment of gastric cancer with Traditional Chinese Medicine (TCM).
MKN45 cells were pre-treated with DHM (0,10,20,30,40,50 μmol/L) for 24 and 48 hours respectively. Cell viability treated with different concentrations of DHM was detected by Cell Counting kit (CCK-8) assay, cell migration was measured by wound healing assay, and cell invasion was tested by Transwell assay. Cells were pre-treated with DHM or co-treated with c-Jun N-terminal kinase (JNK) pathway inhibitor SP600125, then, the levels of migration- and invasion-related proteins were tested by Western blot.
DHM concentration-dependently inhibited cell migration and invasion and downregulated matrix metalloprotein -2 (MMP-2) and phosphorylated JNK (pJNK) expression in MKN45 cells, followed by upregulation of E-cadherin and downregulation of Vimentin. Co-treatment with DHM and JNK inhibitor SP600125 further suppressed MMP-2 expression and cell invasion in MKN45 cells, suggesting that DHM inhibited MKN45 cells metastasis through JNK/MMP-2 pathway.
DHM can inhibit cell migration and invasion in human gastric cancer MKN45 cells through downregulating MMP-2 expression via JNK signaling pathway and reverse epithelial-mesenchymal transition (EMT), implying that DHM could have the potential to serve as an anti-metastatic agent for treating gastric cancer.
探讨二氢杨梅素（DHM）对人胃癌MKN45细胞迁移和侵袭的影响及其机制，为中医药防治胃癌提供实验依据。
将MKN45细胞分别用DHM（0、10、20、30、40、50 μmol/L）预处理24小时和48小时。采用细胞计数试剂盒（CCK-8）检测不同浓度DHM处理后的细胞活力，采用划痕愈合试验检测细胞迁移能力，采用Transwell试验检测细胞侵袭能力。细胞先用DHM预处理或与c-Jun氨基末端激酶（JNK）通路抑制剂SP600125共同处理，然后用蛋白质免疫印迹法检测迁移和侵袭相关蛋白的水平。
DHM浓度依赖性地抑制MKN45细胞的迁移和侵袭，下调基质金属蛋白酶-2（MMP-2）和磷酸化JNK（pJNK）的表达，随后上调E-钙黏蛋白并下调波形蛋白。DHM与JNK抑制剂SP600125共同处理进一步抑制MKN45细胞中MMP-2的表达和细胞侵袭，表明DHM通过JNK/MMP-2通路抑制MKN45细胞转移。
DHM可通过JNK信号通路下调MMP-2表达，抑制人胃癌MKN45细胞的迁移和侵袭，并逆转上皮-间质转化（EMT），这意味着DHM有可能成为治疗胃癌的抗转移药物。
