实用医学杂志2024，Vol.40Issue(1)：59-64,71,7.DOI:10.3969/j.issn.1006-5725.2024.01.011
大黄素抑制胃癌AGS细胞YAP1、FOXD1基因表达及相关机制
The mechanism of emodin inhibiting YAP1 and FOXD1 in gastric cancer AGS cells and its related study
摘要
Abstract
Objective To explore the possible mechanism of emodin in inhibiting proliferation,migration,and invasion of AGS cells and in suppressing the expressions of YAP1 and FOXD1.Methods Normal gastric cell GES-1 and gastric cancer cell AGS were cultured with different concentrations of emodin.CCK8 test,scratch test and Transwell assay were used to verify changes in the biological phenotype of AGS cells.TCGA database was applied to analyze expressions of HK2,YAP1 and FOXD1 in gastric cancer tissues and normal gastric tissues.Western blotting method was used to detect the impacts of emodin on HK2,YAP1 and FOXD1 proteins in AGS cells.Exogenous pyruvic acid was added to verify the changes in YAP1 and FOXD1.Results The IC50 of emodin was significantly higher in GES-1 cells than in AGS cells(P<0.05).CCK8 proliferation test,scratch test,and Transwell assay showed that emodin significantly inhibited the biological abilities of AGS(P<0.05 for comparisons).Analysis on the TCGA bioinformatics database found that the expression of key enzymes HK2 in the glycolysis pathway and oncogenes YAP1 and FOXD1 was significantly higher in gastric cancer tissues than in normal gastric tissues(P<0.05 for comparisons).Emodin significantly inhibited the protein expressions of key glycolytic enzymes HK2 and oncogenes YAP1 and FOXD1(P<0.05 for comparisons).With supplement of exogenous glycolytic metabolite pyruvate,the protein expressions of oncogenes YAP1 and FOXD1 significantly increased(P<0.05 for comparisons).Conclusions Emodin has a significant pharmacological inhibitory effect on gastric cancer AGS cells,markedly suppressing their biological phenotype.Emodin not only significantly inhibits the key enzyme HK2 in glycolysis metabolism,but also the protein expressions of oncogenes YAP1 and FOXD1.With the addition of exogenous pyruvate to enhance the glycolytic metabolic pathway,the protein expressions of oncogenes YAP1 and FOXD1 significantly increased.The above results suggest a close association of YAP1 and FOXD1 with glycolytic metabolism.Emodin may inhibit oncogenes YAP1 and FOXD1 through the glycolytic metabolism of gastric cancer AGS cells.关键词
大黄素/胃癌/HK2/YAP1/FOXD1/糖酵解代谢Key words
emodin/gastric cancer/HK2/YAP1/FOXD1/glycolytic metabolism分类
医药卫生引用本文复制引用
顾天,刘春宏,张飞,钱薇,朱艳秋,褚明亮,刘杰民..大黄素抑制胃癌AGS细胞YAP1、FOXD1基因表达及相关机制[J].实用医学杂志,2024,40(1):59-64,71,7.基金项目
国家自然科学基金(编号:81560088,82060850) （编号:81560088,82060850）
贵州省科技厅基金(编号:黔科合基础-ZK[2022]一般520) （编号:黔科合基础-ZK[2022]一般520）
贵州省高层次创新型人才基金(编号:黔科合平台人才[2020]6016) （编号:黔科合平台人才[2020]6016）
贵州省卫健委基金(编号:gzwkj2021-056,gzwkj2023-453) （编号:gzwkj2021-056,gzwkj2023-453）
贵阳市科技局基金(编号:筑科合同[2022]-4-3-3) （编号:筑科合同[2022]-4-3-3）
贵州省高等学校工程研究中心项目(编号:黔教技[2023]037号) （编号:黔教技[2023]037号）
