Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, China; Anhui Public Health Clinical Center, Hefei 230032, China.
Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
Int Immunopharmacol. 2024 Dec 5;142(Pt B):113194. doi: 10.1016/j.intimp.2024.113194. Epub 2024 Sep 20.
Hepatocellular carcinoma (HCC) is a complex disease, further exacerbated by coexisting diabetes. With the rising incidence of HCC-diabetes cases, alternative treatment strategies are urgently needed. Traditional Chinese Medicine (TCM) offers promising options, and quercetin, a bioactive flavonoid, has shown significant antitumor and antidiabetic effects. This study aimed to investigate the efficacy of quercetin in treating HCC with diabetes using bioinformatics and network pharmacology. We constructed a prognostic model for HCC-diabetes using multivariate Cox proportional hazards regression and identified potential targets for quercetin by intersecting quercetin target genes with HCC-diabetes genes. Molecular docking and molecular dynamics simulations screened these potential targets, and in vitro experiments verified quercetin's targets and pathways. The results revealed a prediction model with four essential genes that effectively predict HCC prognosis in diabetic patients. IL6 and MMP9 were identified as potential targets of quercetin through molecular docking and dynamics simulations. In vitro experiments revealed that quercetin promotes apoptosis, inhibits cell proliferation, and suppresses epithelial-mesenchymal transition (EMT) in HepG2 cells under high-glucose conditions by reducing IL6 expression and inhibiting the MEK/ERK pathway. In summary, quercetin may delay the progression of HCC-diabetes by modulating IL6 to inhibit the MEK/ERK signaling pathway, thereby promoting apoptosis and inhibiting the proliferation and EMT of HepG2 cells.
肝细胞癌（HCC）是一种复杂的疾病，合并糖尿病后病情进一步恶化。随着 HCC-糖尿病病例的发病率不断上升，迫切需要替代治疗策略。传统中药（TCM）提供了有希望的选择，而槲皮素作为一种生物活性类黄酮，已显示出显著的抗肿瘤和抗糖尿病作用。本研究旨在使用生物信息学和网络药理学研究槲皮素治疗 HCC-糖尿病的疗效。我们使用多变量 Cox 比例风险回归构建了 HCC-糖尿病的预后模型，并通过将槲皮素靶基因与 HCC-糖尿病基因相交，确定了槲皮素的潜在靶标。分子对接和分子动力学模拟筛选了这些潜在靶点，并通过体外实验验证了槲皮素的靶标和通路。结果揭示了一个包含四个关键基因的预测模型，该模型可有效预测糖尿病患者的 HCC 预后。通过分子对接和动力学模拟，IL6 和 MMP9 被鉴定为槲皮素的潜在靶标。体外实验表明，槲皮素通过降低 IL6 表达并抑制 MEK/ERK 信号通路，在高葡萄糖条件下促进 HepG2 细胞凋亡、抑制细胞增殖和抑制上皮间质转化（EMT）。综上所述，槲皮素可能通过调节 IL6 抑制 MEK/ERK 信号通路，从而促进 HepG2 细胞凋亡、抑制增殖和 EMT，从而延缓 HCC-糖尿病的进展。
