口腔鳞状细胞癌（OSCC）是一种恶性肿瘤，发病率高且预后不良。胡瓜苦瓜素B（CuB）是一种从葫芦科和十字花科等植物中提取的四环三萜小分子化合物，具有强大的抗癌作用。然而，CuB对于OSCC的作用和机制尚不明确。本研究利用网络药理学分析了CuB和OSCC之间的关系。网络药理学分析显示，CuB和OSCC共享134个靶点，其中PIK3R1、SRC、STAT3、AKT1和MAPK1是关键靶点。分子对接分析显示，CuB与五个靶蛋白结合。富集分析结果显示，CuB通过多条通路对OSCC产生作用，其中PI3K-AKT通路是最重要的通路。体外细胞实验证明，CuB可以抑制SCC25和CAL27细胞的增殖和迁移，阻断细胞周期在G2期，诱导细胞凋亡，并调节PI3K-AKT信号通路的蛋白表达。体内动物实验证明，CuB可以抑制4NQO诱导的小鼠口腔癌。因此，网络药理学、分子对接、细胞实验和动物实验证明，CuB可以通过调节多个靶点和通路发挥在OSCC中的作用。©2023. 作者, 约定许可给 Springer Nature Switzerland AG.

Oral squamous cell carcinoma (OSCC) is a malignant tumor with a high incidence and poor prognosis. Cucurbitacin B (CuB) is a tetracyclic triterpenoid small-molecule compound extracted from plants, such as Cucurbitaceae and Brassicaceae, which has powerful anticancer effects. However, the effect and mechanism of CuB on OSCC remain unclear. Within the framework of the current study, network pharmacology was used to analyze the relationship between CuB and OSCC. The network pharmacology analysis showed that CuB and OSCC share 134 common targets; among them, PIK3R1, SRC, STAT3, AKT1, and MAPK1 are the key targets. The molecular docking analysis showed that CuB binds five target proteins. The results of the enrichment analysis showed that CuB exerted effects on OSCC through various pathways; of these pathways, PI3K-AKT was the most important pathway. The results of the in vitro cell experiments showed that CuB could inhibit the proliferation and migration of SCC25 and CAL27 cells, block the cell cycle in the G2 phase, induce cell apoptosis, and regulate the protein expression of the PI3K-AKT signaling pathway. The results of the in vivo animal experiments showed that CuB could inhibit 4NQO-induced oral cancer in mice. Therefore, network pharmacology, molecular docking, cell experiments, and animal experiments showed that CuB could play a role in OSCC by regulating multiple targets and pathways.© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.