舌鳞状细胞癌 (TSCC) 是头颈部鳞状细胞癌最常见的形式，约占所有口腔癌的三分之一。重楼（PP）表现出有希望的抗肿瘤特性，但其潜在机制仍难以捉摸。本研究为PP治疗TSCC的分子机制提供了新的见解，并为其临床应用奠定了理论基础。采用转录组学和网络药理学方法，我们鉴定了与PP作用相关的自噬相关关键基因。对这些基因进行KEGG和GO富集分析以确定其相关功能。在体外，用 10、30 和 60 μg/ml 的 PP 处理 CAL-27 细胞 24 小时，以评估肿瘤细胞增殖、凋亡和自噬相关标志物。 MAPK3 和 PSEN1 与 PP 的分子对接显示稳定的氢键相互作用，表明这些皂苷通过自噬途径在 TSCC 中具有治疗潜力。体外实验表明PP能显着抑制舌鳞状细胞癌CAL-27细胞的增殖活性并促进肿瘤细胞凋亡。 Western blot分析证实治疗后自噬标志物P62、LC3B和Beclin1的表达发生变化，表明自噬途径被激活。我们的结果表明PP通过自噬途径抑制肿瘤细胞，其中MAPK3和PSEN1发挥了潜在作用功能分子。© 2024。作者。

Tongue squamous cell carcinoma (TSCC) represents the most prevalent form of head and neck squamous cell carcinomas, comprising approximately one-third of all oral cancers. Paris polyphylla(PP) exhibit promising anti-tumor properties, yet their underlying mechanisms remain elusive. This study offers novel insights into the molecular mechanisms underlying TSCC treatment with PP and establishes a theoretical basis for their clinical application.Employing transcriptomics and network pharmacology methodologies, we identified autophagy-related key genes associated with the effects of PP. These genes were subjected to KEGG and GO enrichment analyses to determine their related functions. In vitro, CAL-27 cells were treated with 10, 30, and 60 μg/ml of PP for 24 h to assess tumor cell proliferation, apoptosis, and autophagy-related markers.Molecular docking of MAPK3 and PSEN1 with PP revealed stable hydrogen bond interactions, indicating the therapeutic potential of these saponins in TSCC through the autophagy pathway. In vitro experiments demonstrated significant inhibition of proliferative activity in tongue squamous carcinoma CAL-27 cells and promotion of tumor cell apoptosis by PP. Western blot analysis confirmed alterations in the expression of autophagy markers P62, LC3B, and Beclin1 following treatment, suggesting activation of the autophagy pathway.Our results suggest that PP inhibits tumor cells through the autophagy pathway, in which MAPK3 and PSEN1 play a role as potential functional molecules.© 2024. The Author(s).