Role and Mechanism of Scopoletin in Regulating HIF‐1α/BNIP3 Cascade to Mediate Autophagy in Lung Cancer Proliferation and Metastasis

Alkaloids may offer significant advantages over other anticancer drugs, but the role of scopoletin in treating lung cancer is still not understood. A549 cells were treated with 6.12 μM scopoletin or 25 μg/mL 5-fluorouracil as positive drugs for 24 h. CCK-8 assay and colony formation assay were performed to assess the effect of scopoletin on A549 cell proliferation, along with flow cytometry to analyze apoptosis, and Transwell and cell scratch assays to detect invasion and migration. Autophagy-associated markers Beclin1, LC3B-II/LC3B-I, and p62 were measured by Western Blot. A mouse model of LC was established by injecting A549 cells subcutaneously, with HE staining used to evaluate pathology and IHC employed to detect HIF-1α and BNIP3 expression in the xenograft tumors. Scopoletin induced apoptosis in A549 cells by facilitating autophagy and prevented invasion and migration. Inhibiting autophagy decreased the antitumor efficacy of scopoletin. In A549 cells and LC mouse models, scopoletin triggered the HIF-1α/BNIP3 cascade. Inhibition of the HIF-1α/BNIP3 pathway somewhat negated scopoletin's effects on A549 cell growth and metastasis, and on the progression of LC in mice. Scopoletin mediates autophagy to intervene in LC proliferation and metastasis by regulating the HIF-1α/BNIP3 cascade.