Wu Yuche, Wang Bing, Mao Xuwen, Chen Wei, Akber Aisa Haji
Xinjiang Technical Institute of Physics and Chemistry Chinese Academy of Sciences, Urumqi, Xinjiang, China.
The Fourth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
Front Pharmacol. 2025 May 13;16:1526952. doi: 10.3389/fphar.2025.1526952. eCollection 2025.
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).
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.
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.
本研究旨在探讨骆驼蓬碱衍生物B-9-3抑制非小细胞肺癌（NSCLC）血管生成并促进其细胞凋亡的分子机制。
建立三种非小细胞肺癌（NSCLC）模型（人NSCLC细胞系A549、人肺鳞癌细胞系H226、人肺大细胞癌细胞系H460）。使用CCK-8法和集落形成试验评估细胞增殖。通过划痕伤口愈合、侵袭和迁移试验评估细胞运动能力。通过Hoechst 33258染色、AO/EB荧光染色和流式细胞术分析细胞凋亡。采用实时定量PCR检测B细胞淋巴瘤/白血病-2（Bcl-2）、Bcl-2相关X蛋白（Bax）和半胱天冬酶-3（Caspase-3）的mRNA表达，同时进行蛋白质免疫印迹法评估血管内皮生长因子A（VEGFA）、磷脂酰肌醇3激酶p110β（PI3K）、磷酸化磷脂酰肌醇3激酶（p-PI3K）、蛋白激酶B（AKT）、磷酸化蛋白激酶B（p-AKT）、Bax、Bcl-2和Caspase-3的蛋白水平。
与对照组相比，B-9-3（50、100、200μg/mL）抑制了三种肺癌细胞的生长和运动能力，抑制细胞侵袭和迁移，并促进细胞凋亡和坏死。三种非小细胞肺癌（NSCLC）细胞的凋亡率显著增加。Bax和Caspase-3的mRNA表达明显上调，而Bcl-2的表达明显下调。此外，VEGFA、p-PI3K/PI3K、p-AKT/AKT和Bcl-2的蛋白水平显著降低，而Bax和Caspase-3的蛋白水平显著升高。
骆驼蓬碱衍生物B-9-3可能通过VEGFA/PI3K/AKT信号通路抑制血管生成并促进肺癌细胞凋亡，从而发挥其抗NSCLC作用。
