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Traditional Chinese Medicine (TCM) is renowned for its holistic treatment approach and minimal side effects. Luteolin (LUT) and Quercetin (QUE) each possess notable anticancer properties. This study is the first to elucidate the synergistic anticancer activity of the combination of LUT and QUE (LUT+QUE) against lung cancer. The synergistic anticancer activity of QUE+LUT was evaluated through the combination index (CI) value by varying the concentrations of QUE and LUT. Network pharmacology analysis was then employed to identify the key targets and crucial signaling pathways for QUE and LUT. Finally, the synergistic anticancer mechanisms of QUE+LUT were elucidated by verifying these core targets and pathways through various experiments, including apoptosis assays, migration assays, ELISA, Western blot and reactive oxygen species (ROS) assays. The key targets identify through network pharmacology analysis include BCL2L1, MMP9, JUN, PTGS2, TP53, AKT1 and CASP3. The crucial pathways are the PI3K-Akt signaling pathway and chemically-induce carcinogenic ROS pathways. Cellular experiments demonstrate that QUE+LUT synergistically induce apoptosis, inhibit cell proliferation, migration and invasion, increase ROS levels and regulate the PI3K-Akt signaling pathway, effectively targeting lung cancer cells. The combined therapy of QUE and LUT holds potential as an effective treatment for cancer patients, providing valuable insights for the selection and mechanistic exploration of important anticancer drugs.
Wang et al. (Thu,) studied this question.