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<p>Liver cancer is the malignancy with the highest mortality rate among digestive system cancers worldwide. Flavonoid plant extracts have shown significant safety and extensive function, especially anti-tumor activity. In this study, the therapeutic effects of a combination of baicalein and luteolin were evaluated <i>in vitro</i>. Cell proliferation, migration, and apoptosis were performed respectively through MTT assay, clone formation, wound healing, transwell, and JC-1 staining. Protein levels of EGFR, p-ERK, NFκB, and cleaved-caspase3 via western blotting and the interaction with key proteins EGFR and NFκB by molecular docking were determined in order to explore the underlying mechanism. In addition, a mouse heterotopic transplant tumor model was established to assess the anticancer activity <i>in vivo</i>. The experimental results showed that the combination of baicalein and luteolin exhibited more potent in suppressing cell proliferation and migration and inducing cell apoptosis when compared with baicalein or luteolin. The western blot and molecular docking studies demonstrated that the potential mechanism may relate to the inhibiting of the EGFR/NFκB signaling pathway. Moreover, the HepG2 cell xenograft model, hematoxylin and eosin, and immunohistochemical staining results also confirmed that the combination of baicalein and luteolin was more effective than a single compound in inhibiting tumor growth. In summary, the combination of baicalein and luteolin may resist the proliferation, migration, and apoptosis activity of HepG2 cells through the EGFR/NFκB signaling pathway, which provides new insights for further exploring plant extract treatment for liver cancer.</p>

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Synergistic Effect of Baicalein Combined With Luteolin by Inhibiting the EGFR/NFκB Signaling Pathway in Hepatocellular Carcinoma Cells

  • 期刊论文

  • 发表日期：

    2026年2月1日

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  • Qizhu Feng,
  • Manman Lu,
  • Qi Wang,
  • Jie Sun,
  • Jian Zhang,
  • Chao Zhang

摘要

Liver cancer is the malignancy with the highest mortality rate among digestive system cancers worldwide. Flavonoid plant extracts have shown significant safety and extensive function, especially anti-tumor activity. In this study, the therapeutic effects of a combination of baicalein and luteolin were evaluated in vitro. Cell proliferation, migration, and apoptosis were performed respectively through MTT assay, clone formation, wound healing, transwell, and JC-1 staining. Protein levels of EGFR, p-ERK, NFκB, and cleaved-caspase3 via western blotting and the interaction with key proteins EGFR and NFκB by molecular docking were determined in order to explore the underlying mechanism. In addition, a mouse heterotopic transplant tumor model was established to assess the anticancer activity in vivo. The experimental results showed that the combination of baicalein and luteolin exhibited more potent in suppressing cell proliferation and migration and inducing cell apoptosis when compared with baicalein or luteolin. The western blot and molecular docking studies demonstrated that the potential mechanism may relate to the inhibiting of the EGFR/NFκB signaling pathway. Moreover, the HepG2 cell xenograft model, hematoxylin and eosin, and immunohistochemical staining results also confirmed that the combination of baicalein and luteolin was more effective than a single compound in inhibiting tumor growth. In summary, the combination of baicalein and luteolin may resist the proliferation, migration, and apoptosis activity of HepG2 cells through the EGFR/NFκB signaling pathway, which provides new insights for further exploring plant extract treatment for liver cancer.