Abstract
BACKGROUND: Liriopesides B (LPB), a steroidal saponin derived from Liriope spicata, demonstrates potent anti-tumor activity across multiple malignancies. Nevertheless, its influence on oral squamous cell carcinoma (OSCC) has not been investigated. This study aims to evaluate the anti-OSCC properties of LPB and elucidate the underlying mechanisms. METHODS: Proliferation of OSCC cells treated with LPB was evaluated via Cell Counting Kit-8 (CCK-8) and colony formation assays. Cell migration, invasion, and apoptosis were analyzed, along with measuring related gene expression utilizing quantitative reverse transcription polymerase chain reaction (qRT-PCR). Transcriptomic analysis of LPB-treated cells was performed, and protein levels within the PI3K/Akt/mTOR cascade were examined by Western blotting. In vivo anti-cancer activity of LPB was assessed through xenograft tumor models, with messenger RNA (mRNA) levels of MMP-2/9, Bcl-2, Bax, and Bad assessed by qRT-PCR, and PI3K/Akt/mTOR pathway protein expression analyzed via immunohistochemistry (IHC). Biological safety was evaluated by body weight changes of nude mice, Hematoxylin and Eosin (H&E) staining and serum biochemical markers. RESULTS: LPB suppressed OSCC cell growth, colony formation, motility, and invasiveness while promoting apoptosis. High-throughput sequencing suggested that the PI3K/Akt cascade is a potential target of LPB in OSCC. Treatment with LPB markedly suppressed key protein levels within the PI3K/Akt/mTOR cascade. In xenograft models, LPB treatment led to considerable decreases in tumor volume and weight. Furthermore, mRNA levels of MMP-2/9 and proteins such as PI3K, Akt, p-mTOR, and S6 were markedly downregulated in LPB-treated tumors, while Bax and Bad expression were upregulated. No substantial variations in body weight, histological morphology, or organ function were observed between the control and LPB-treated cohorts. CONCLUSIONS: LPB exerts anti-OSCC properties by modulating the PI3K/Akt/mTOR cascade with minimal biological toxicity, highlighting its potential as a therapeutic agent for OSCC.