Ginkgetin inhibits non-small cell lung cancer via the HSP90-AKT signaling pathway

Area of Science:

• Pharmacology
• Oncology
• Computational Biology

Background:

• Lung cancer (LC) is a leading cause of cancer mortality worldwide.
• Ginkgetin (GK), a flavonoid from Ginkgo biloba, possesses known anti-tumor activities.
• Non-small cell lung cancer (NSCLC) remains a significant therapeutic challenge.

Purpose of the Study:

• To investigate the molecular targets and mechanisms of Ginkgetin (GK) in non-small cell lung cancer (NSCLC) therapy.
• To integrate network pharmacology with in vitro cellular experiments.
• To provide a scientific basis for GK as a potential NSCLC therapeutic agent.

Main Methods:

• Network pharmacology analysis to identify potential targets and pathways.
• Molecular docking and molecular dynamics (MD) simulations for binding affinity assessment.
• In vitro cellular experiments to evaluate GK's effect on NSCLC cell lines (A549 and LLC).

Main Results:

• Network pharmacology identified 52 potential targets, 5 key proteins, and 113 signaling pathways for GK against NSCLC.
• Molecular simulations confirmed tight binding between GK and key proteins, notably EGFR.
• Cellular experiments demonstrated that GK significantly suppresses proliferation and metastasis in A549 and LLC cells.
• Elevated HSP90AA1 levels were observed in NSCLC, suggesting its role in the disease.

Conclusions:

• Ginkgetin (GK) exhibits significant anti-NSCLC effects by inhibiting cell proliferation and metastasis.
• The anti-cancer mechanism of GK likely involves the HSP90-AKT signaling pathway.
• These findings support further research into GK as a novel therapeutic strategy for NSCLC.