Introduction: Tongue Squamous Cell Carcinoma (TSCC) is a prevalent head and neck malignancy with limited targeted therapies and minimal toxicity. Sodium Cantharidate (SCA), a natural compound, exhibits anti-tumor potential, but its molecular targets in TSCC remain undefined. This study aimed to evaluate SCA's anti-TSCC efficacy in preclinical mod-els and elucidate its mechanism of action. Methods: SCA's effects on TSCC cells were assessed using CCK-8 viability, scratch wound healing, Transwell migration/invasion, and flow cytometry (apoptosis). Efficacy was further evaluated in nude mouse xenograft models and patient-derived TSCC organoids. Molecular mechanisms were investigated via Western blotting. Results: SCA significantly inhibited TSCC cell proliferation, migration, and invasion, and induced dose-dependent apoptosis in vitro. It demonstrated cytotoxicity in xenografts and or-ganoids. Western blotting showed SCA upregulated p53 protein and phosphorylation at Ser33, Ser37, and Ser46. Pro-apoptotic BAX and cleaved Caspase 3 increased, while anti-apoptotic BCL-2 decreased, significantly lowering the BCL-2/BAX ratio. Discussion: SCA attenuates TSCC growth and invasion in vitro and in vivo, primarily by inducing apoptosis through modulation of p53 phosphorylation. This is the first study to vali-date SCA's efficacy using patient-derived TSCC organoids, highlighting their value for pre-clinical drug assessment. While promising, further mechanistic depth is warranted. The results support SCA's potential for clinical translation. Conclusion: SCA potently inhibits TSCC progression in cell lines, xenografts, and patient-derived organoids. Its mechanism involves activation of p53 phosphorylation, shifting the BCL-2/BAX balance, and triggering caspase-dependent apoptosis. These findings position SCA as a promising therapeutic candidate and underscore the utility of organoid models in oncology drug development.
Li et al. (Thu,) studied this question.