Cancer Institute, Fourth Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China.
Drug Des Devel Ther. 2022 Jul 29;16:2423-2436. doi: 10.2147/DDDT.S370114. eCollection 2022.
To explore the mechanism of the effect of baicalein on radioresistance of esophageal cancer, and to provide ideas for the treatment of patients with poor radiotherapy effect of esophageal cancer.
The glycolytic rate assay kit was used to detect the changes in glycolytic metabolism in esophageal cancer cells after treatment with baicalein, and mass spectrometry was used to detect whether baicalein could affect the level of glycolysis-related metabolites in esophageal cancer cells. The binding of baicalein to the target protein was simulated by molecular docking technique, the protein expression level was detected by Western Blot, and the changes in the cell cycle were detected by flow cytometry.
Radiation combined with baicalein could significantly inhibit the proliferation and migration of esophageal cancer cells compared with that of 6 Gy rays alone. The results of the glycolytic rate assay showed that baicalein could inhibit the glycolysis of esophageal cancer cells. Metabonomic studies showed that baicalein could affect the expression levels of glycolysis-related metabolites. The results of network pharmacology showed that baicalein could target several key glycolysis enzymes and glycolysis-related proteins, such as HIF-1A. The results of the WB experiment showed that glycolysis-related proteins and cycle-related proteins were down-regulated after baicalein treatment.
The main mechanism of baicalein inhibiting radiation resistance of esophageal cancer cells is that targeting HIF-1A protein regulates glucose metabolism and then regulates Cyclin D1/CDK4 axis to change the cell cycle.
探讨黄芩素对食管癌放射抗拒的作用机制，为治疗食管癌放疗效果不佳的患者提供思路。
采用糖酵解速率检测试剂盒检测黄芩素处理后食管癌细胞糖酵解代谢的变化，采用质谱技术检测黄芩素是否影响食管癌细胞中糖酵解相关代谢物的水平。采用分子对接技术模拟黄芩素与靶蛋白的结合，采用 Western Blot 检测蛋白表达水平，采用流式细胞术检测细胞周期的变化。
与单纯 6 Gy 射线照射相比，辐射联合黄芩素可显著抑制食管癌细胞的增殖和迁移。糖酵解速率检测结果表明黄芩素可抑制食管癌细胞的糖酵解。代谢组学研究表明黄芩素可影响糖酵解相关代谢物的表达水平。网络药理学研究表明黄芩素可靶向几个关键的糖酵解酶和糖酵解相关蛋白，如 HIF-1A。WB 实验结果表明黄芩素处理后糖酵解相关蛋白和周期相关蛋白下调。
黄芩素抑制食管癌细胞放射抗拒的主要机制是通过靶向 HIF-1A 蛋白调节葡萄糖代谢，进而调节 Cyclin D1/CDK4 轴改变细胞周期。
