Physalin A Suppresses Human Oral Squamous Carcinoma Cell Migration and Invasion Through Inhibiting Grb2/Ras and MMP/uPA Signaling Pathways

Background/Aim: Oral squamous cell carcinoma (OSCC) has a nearly 50% global mortality. Physalin A (PA) shows anti-cancer activities, but its role in metastasis remains unclear in OSCC cells. This study intended to determine whether PA inhibits OSCC cell migration and invasion and to clarify the underlying mechanisms. Materials and Methods: HSC-3 OSCC cells were analyzed using wound-healing, migration, and invasion assays. Atomic force microscopy (AFM) was used to assess morphological changes. Western blotting examined E-cadherin (E-cad), matrix metalloproteinases (MMPs), and urokinase plasminogen activator (uPA). A RasV12/scrib−/− Drosophila model evaluated in vivo tumor suppression. Results: PA significantly reduced wound closure, migration, and invasion in HSC-3 cells. AFM showed decreased cancer-related morphological alterations. PA increased E-cadherin and reduced MMPs and uPA. PA also inhibited growth factor receptor-bound protein 2 (Grb2)/Ras and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor-kappa B (NF-kB) signaling. In vivo, PA suppressed tumor formation and metastasis in RasV12/scrib−/− genotype Drosophila. Conclusion: PA attenuates HSC-3 OSCC cell migration and invasion by regulating Grb2/Ras, PI3K/Akt/NF-kB, and MMP/uPA pathways, suggesting its potential as an anti-metastatic agent for OSCC.