Hubei Engineering Technology Research Center of Chinese Materia Medica Processing, College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China.
Biofactors. 2022 Jul;48(4):883-896. doi: 10.1002/biof.1826. Epub 2022 Feb 3.
Daidzin (DDZ) is a natural brassin-like compound extracted from the soybean, and has been found to have therapeutic potential against tumors in recent years. This study investigates the therapeutic effect of DDZ on hepatocellular carcinoma cells and elucidates the possible mechanisms of action. The viability of HCCLM3 and Hep3B cells was detected by MTT assay. Western blots and qPCR were used to detect the protein and mRNA levels of proliferation and apoptosis related genes. Gas chromatography-mass spectrometry (GC-MS) was used for metabolome analysis. In vivo antitumor effects were assessed in nude mice engrafted with HCC cell lines. Our results show that DDZ treatment dose-dependently inhibited cell viability, migration, and survival. The expressions of CDK1, BCL2, MYC, and survivin were reduced, while the expressions of BAX and PARP were increased in DDZ treated cells. The differentially expressed metabolites detected in DDZ treated cultures are associated with glycolysis/gluconeogenesis pathways. Bioinformatic analysis identified TPI1, a gene in the glycolysis pathway with prognostic value for hepatocellular carcinoma (HCC), and DDZ treatment downregulated this gene. In vivo experiments show that DDZ significantly reduced the tumor volume and weight, and inhibited Ki67 expression within tumors. This study shows that DDZ interfered with the survival and migration of hepatocellular carcinoma cells, likely via TPI1 and the gluconeogenesis pathway.
大豆中提取的天然拟南芥素化合物大豆苷元（DDZ）近年来被发现具有抗肿瘤的治疗潜力。本研究探讨了 DDZ 对肝癌细胞的治疗作用，并阐明了其可能的作用机制。MTT 法检测 HCCLM3 和 Hep3B 细胞的活力。Western blot 和 qPCR 检测增殖和凋亡相关基因的蛋白和 mRNA 水平。气相色谱-质谱联用（GC-MS）进行代谢组学分析。裸鼠荷瘤实验评估体内抗肿瘤作用。结果表明，DDZ 处理剂量依赖性地抑制细胞活力、迁移和存活。DDZ 处理细胞中 CDK1、BCL2、MYC 和 survivin 的表达降低，BAX 和 PARP 的表达增加。DDZ 处理培养物中检测到的差异表达代谢物与糖酵解/糖异生途径有关。生物信息学分析鉴定了糖酵解途径中与肝癌（HCC）预后相关的 TPI1 基因，DDZ 处理下调了该基因。体内实验表明，DDZ 显著降低了肿瘤体积和重量，并抑制了肿瘤内 Ki67 的表达。本研究表明，DDZ 干扰了肝癌细胞的存活和迁移，可能通过 TPI1 和糖异生途径。
