Ginkgolide B inhibits non-small cell lung cancer cells by modulating the integrin β3 pathway

  • Toxicol Appl Pharmacol. 2026 Jun:511:117806. doi: 10.1016/j.taap.2026.117806.
Li Shao  1 ,  Zhicheng Song  1 ,  Jialin Cong  1 ,  Jianjun Ma  2 ,  Anye Du  3
Affiliations
  • 1. Department of Integrated Chinese and Western Medicine, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, China.
  • 2. Department of Oncology, 970th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, Yantai 264002, China.
  • 3. Department of Integrated Chinese and Western Medicine, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, China. Electronic address: [email protected].
PMID: 41921594 DOI: 10.1016/j.taap.2026.117806
Abstract

Objective: Ginkgolide B (GB) exhibits anti-tumor activity. However, the inhibitory effect of GB on non-small cell lung Cancer (NSCLC) and its specific molecular mechanisms remain unclear. This study aimed to analyze the pharmacological mechanism of GB for NSCLC.

Methods: Two NSCLC cells, A549 and H1299, were treated with different doses of GB for 48 h. Cell Apoptosis, cell viability, and Integrin β3 expression were measured to analyze the inhibitory effect of GB. The binding affinity between GB and Integrin β3 was analyzed using microscale thermophoresis (MST). An Integrin αvβ3 blocker, LM609, was used as a positive control to analyze the effects of GB on Integrin αvβ3. Meanwhile, the silence of Integrin β3 (ITGB3) in NSCLC cells was established by ITGB3 siRNA transfection to analyze the role of Integrin β3 in GB-mediated inhibition. Changes in cell viability, Integrin β3, and the Akt/PI3K/mTOR pathway were measured. In A549-injected nude mice, Animals were treated with GB or LM609 to observe the changes in tumor growth, Integrin β3, and the Akt/PI3K pathway.

Results: GB treatment promoted the Apoptosis of NSCLC cells, inhibited cell viability, and suppressed the Integrin β3 expression in a dose-dependent manner. Meanwhile, a good binding affinity was found between GB and Integrin β3. GB or LM609 treatment not only inhibited the Integrin αvβ3 expression but also suppressed the phosphorylation of the Akt/PI3K pathway. Meanwhile, the silence of Integrin β3 attenuated the GB-induced effects. In vivo, GB treatment suppressed tumor growth, as well as suppressed the Integrin β3 expression and the phosphorylation of the Akt/PI3K pathway.

Conclusions: GB inhibited NSCLC by inhibiting the Integrin β3 pathway, providing a theoretical basis for the application of GB in NSCLC.

Keywords
Ginkgolide B; Integrin β3; NSCLC; The Akt/PI3K pathway.
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