Background: Oral squamous cell carcinoma (OSCC) is one of the most common cancers, with high metastasis and mortality. Licochalcone A (LCA) is a chalconoid from the root of Glycyrrhiza inflata , which has anti-tumor, anti-inflammatory, anti-angiogenesis effects in many cancers. However, the mechanism that underlies LCA regulating cell proliferation, migration, and invasion in OSCC remains poorly understood.
Methods: LY294002 or insulin-like growth factor 1 (IGF-1) were used to block or stimulate the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) pathway in OSCC cells. Cell proliferation was investigated by MTT assay and proliferating cell nuclear antigen (PCNA) protein level using Western blot. The expression of metastasis-related protein was detected via Western blot. Cell migration and invasion abilities were evaluated by trans-well assay. A murine xenograft model of OSCC was established to investigate the anti-tumor effect of LCA in vivo.
Results: Treatment of LCA inhibited cell proliferation in SCC4 and CAL-27 cells. Moreover, PI3K/AKT signaling was blocked by LY294002, and activated by IGF-1. LCA could suppress proliferation, migration, and invasion of OSCC cells, which was similar to the treatment of LY294002. In addition, LCA decreased IGF-1-induced OSCC progression. In a murine xenograft model, LCA treatment protected against tumor growth and metastasis in vivo.
Conclusions: LCA might inhibit cell proliferation, migration, and invasion through regulating the PI3K/AKT pathway in OSCC, developing a potential chemotherapeutic agent for OSCC.
Keywords: oral squamous cell carcinoma, Licochalcone A, PI3K/AKT, PCNA, migration, invasion