ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1526952
Harmine derivative B-9-3 inhibits non-small cell lung cancer via the VEGFA/PI3K/AKT pathway
Provisionally accepted
- 1Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences (CAS), Ürümqi, Xinjiang Uyghur Region, China
- 2Fourth Affiliated Hospital, Xinjiang Medical University, Urumqi, China
- 3Department of Pharmacology, School of Pharmacy, Xinjiang Medical University, Urumqi, China
- 4Xinjiang Medical University, Ürümqi, China
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Background: This study aimed to investigate the molecular mechanism by which the Harmine derivative B-9-3 inhibits angiogenesis and promotes apoptosis in non-small cell lung cancer (NSCLC). Methods: Three non-small cell lung cancer (NSCLC) models (human NSCLC cell line A549, human lung squamous cell carcinoma cell line H226, human large cell lung carcinoma cell line H460) were established. Cell proliferation was assessed using CCK-8 assays and colony formation assays. Cell motility was evaluated through scratch wound healing, invasion, and migration assays. Cell apoptosis was analyzed by Hoechst 33258 staining, AO/EB fluorescence staining, and flow cytometry. Real-time PCR was used to measure the mRNA expression of B-cell lymphoma/leukemia-2 (Bcl-2), Bcl-2-associated X protein (Bax), and Caspase-3, while Western blotting was performed to assess the protein levels of vascular endothelial growth factor A (VEGFA), phosphatidylinositol 3-kinases p110 Beta (PI3K), phospho-phosphatidylinositol 3-kinases (p-PI3K), protein kinase B (AKT), phosphorylated protein kinase B (p-AKT), Bax, Bcl-2, and Caspase-3. Results: Compared to the control group, B-9-3 (50, 100, 200 μg/mL) inhibited the growth and motility of the three types of lung cancer cells, suppressed cell invasion and migration, and promoted cell apoptosis and necrosis. The apoptosis rates in three types of non-small cell lung cancer (NSCLC) cells were significantly increased. The mRNA expressions of Bax and Caspase-3 were markedly upregulated, while that of Bcl-2 was significantly downregulated. Additionally, the protein levels of VEGFA, p-PI3K/PI3K, p-AKT/AKT, and Bcl-2 were notably reduced, whereas the protein levels of Bax and Caspase-3 were significantly elevated.The harmine derivative B-9-3 may exert its anti-NSCLC effects by inhibiting angiogenesis and promoting lung cancer cell apoptosis via the VEGFA/PI3K/AKT signaling pathway.
Keywords: harmine derivative B-9-3, Non-small cell lung cancer, Apoptosis, Angiogenesis, VEGFA/PI3K/AKT
Received: 12 Nov 2024; Accepted: 18 Apr 2025.
Copyright: © 2025 Wu, Wang, Mao, Chen and Akber Aisa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: HAJI Akber Aisa, Xinjiang Medical University, Ürümqi, China
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