Li Jiaqi, Wang Zhiyong, Lu Yanxin, Xia Qiang, Wei Pei
Department of Immunology, Zhuhai Campus of Zunyi Medical University, Zhuhai, China.
Dokl Biochem Biophys. 2025 Sep 14. doi: 10.1134/S1607672925600198.
Basic fibroblast growth factor (bFGF) is a potent mitogen implicated in tumor progression, yet its precise role in cancer cell invasion remains multifaceted. Here, we unveiled a dose-dependent, biphasic regulatory effect of bFGF blockade on the invasiveness of lung cancer cells. Using a neutralizing monoclonal antibody against bFGF (bFGF Ab), we demonstrated that moderate neutralization of bFGF inhibited tumor cell invasion. Conversely, excessive bFGF blockade paradoxically enhanced the invasive capacity of lung cancer cells. Furthermore, we showed that the divergent invasive phenotypes arising from varying degrees of bFGF inhibition were mediated by altered vascular endothelial growth factor (VEGF) secretion. These findings underscore the critical importance of dose optimization in bFGF-targeted therapies, particularly concerning their impact on lung cancer invasiveness, and identify VEGF as a key mediator of these effects.
碱性成纤维细胞生长因子(bFGF)是一种与肿瘤进展相关的强效促有丝分裂原,但其在癌细胞侵袭中的确切作用仍具有多面性。在此,我们揭示了bFGF阻断对肺癌细胞侵袭性的剂量依赖性双相调节作用。使用针对bFGF的中和单克隆抗体(bFGF抗体),我们证明适度中和bFGF可抑制肿瘤细胞侵袭。相反,过度阻断bFGF却反常地增强了肺癌细胞的侵袭能力。此外,我们表明不同程度的bFGF抑制所产生的不同侵袭表型是由血管内皮生长因子(VEGF)分泌改变介导的。这些发现强调了在bFGF靶向治疗中剂量优化的至关重要性,特别是关于其对肺癌侵袭性的影响,并确定VEGF是这些效应的关键介质。