Lu Dongdong, Huang Leijie, Weng Chunyan
Department of Gastroenterology, Ningbo No. 2 Hospital, Ningbo, Zhejiang Province, 315000, People's Republic of China.
Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang Province, 310000, People's Republic of China.
Drug Des Devel Ther. 2025 Apr 5;19:2653-2666. doi: 10.2147/DDDT.S504671. eCollection 2025.
Gastric cancer (GC) remains a leading cause of cancer-related mortality, with limited effective treatment options for advanced stages. As a steroidal saponin with documented anti-neoplastic properties in multiple cancers, digitonin's mode of action in GC pathogenesis has yet to be fully elucidated. This research focused on exploring the potential of Digitonin in GC treatment using a combination of network pharmacology and experimental validation.
The inhibitory effects of Digitonin on the proliferation, invasion, and migration of gastric cancer cells were evaluated using CCK-8, colony formation, wound healing, and transwell assays. Key targets of Digitonin were identified through network pharmacology. Molecular docking and various experiments, including Western blot, immunofluorescence, and a subcutaneous xenograft model, were used for validation.
Digitonin exhibited stronger cytotoxicity against GC cells and significantly inhibited GC cell proliferation, migration, and invasion. Network pharmacology analysis revealed that the core targets of Digitonin are involved in key cancer-related signaling pathways, including HIF-1α, Ras, and PI3K-Akt pathways, with HSP90AA1 and NFKB1 identified as central targets. Further molecular docking, Western blotting, and immunofluorescence experiments confirmed that Digitonin significantly suppressed the expression of HSP90AA1 and inhibited the nuclear translocation of NFKB1, inducing cell apoptosis. Additionally, a subcutaneous xenograft model of GC further validated that Digitonin effectively inhibited tumor growth.
Digitonin serves as a promising multi-target therapeutic agent for GC. This study underscores the potential of combining network pharmacology with traditional Chinese medicine to identify novel therapeutic targets and develop effective anti-cancer strategies. In addition, these findings suggest that digitonin could be a promising candidate for future clinical trials in GC treatment.
胃癌（GC）仍然是癌症相关死亡的主要原因，晚期胃癌的有效治疗选择有限。洋地黄皂苷作为一种在多种癌症中具有抗肿瘤特性的甾体皂苷，其在胃癌发病机制中的作用模式尚未完全阐明。本研究聚焦于通过网络药理学和实验验证相结合的方法，探索洋地黄皂苷在胃癌治疗中的潜力。
使用CCK-8、集落形成、伤口愈合和Transwell实验评估洋地黄皂苷对胃癌细胞增殖、侵袭和迁移的抑制作用。通过网络药理学确定洋地黄皂苷的关键靶点。分子对接以及包括蛋白质免疫印迹法、免疫荧光和皮下异种移植模型在内的各种实验用于验证。
洋地黄皂苷对胃癌细胞表现出更强的细胞毒性，并显著抑制胃癌细胞的增殖、迁移和侵袭。网络药理学分析表明，洋地黄皂苷的核心靶点参与关键的癌症相关信号通路，包括HIF-1α、Ras和PI3K-Akt通路，其中HSP90AA1和NFKB1被确定为核心靶点。进一步的分子对接、蛋白质免疫印迹法和免疫荧光实验证实，洋地黄皂苷显著抑制HSP90AA1的表达并抑制NFKB1的核转位，诱导细胞凋亡。此外，胃癌皮下异种移植模型进一步验证了洋地黄皂苷能有效抑制肿瘤生长。
洋地黄皂苷是一种有前景的胃癌多靶点治疗药物。本研究强调了将网络药理学与中药相结合以确定新的治疗靶点和制定有效的抗癌策略的潜力。此外，这些发现表明洋地黄皂苷可能是未来胃癌治疗临床试验的有前景的候选药物。
