Lim Hae-In, Kim Ga Yoon, Choi Yu-Jeong, Lee Kangwook, Ko Seong-Gyu
Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea.
College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul, 08826, Republic of Korea.
Discov Oncol. 2025 Apr 17;16(1):551. doi: 10.1007/s12672-025-02056-7.
Colorectal cancer is a significant global health challenge due to chemoresistance, necessitating new treatments. Cucurbitacin D, with its anti-cancer properties, shows promise, but its effects on colorectal cancer are not well understood. We investigated the impact of cucurbitacin D on colorectal cancer cell lines using MTT assays and Annexin V/7-AAD staining followed by flow cytometry for apoptosis analysis. Public databases helped identify cucurbitacin D and colorectal cancer-related gene targets for network pharmacology analysis. Protein-protein interaction networks were constructed using STRING and analyzed in Cytoscape. Gene ontology and KEGG pathway enrichment analyses were performed using ClueGo. Molecular docking studies were conducted via Autodock Vina and visualized in Discovery Studio. Western blot assessed protein expression changes in key targets under cucurbitacin D. Cucurbitacin D dose-dependently reduced colorectal cancer cell viability and induced apoptosis. Network pharmacology pinpointed crucial targets like STAT3, AKT1, CCND1, and CASP3. Molecular docking confirmed strong interactions with these targets. Enrichment analysis highlighted involvement in the 'PI3K-AKT,' 'JAK-STAT,' and 'ErbB' signaling pathways. These findings suggest cucurbitacin D as a potential anti-colorectal cancer agent, demonstrating significant effects on cell viability and apoptosis, and engaging critical cancer-related pathways, making it a promising candidate for further colorectal cancer therapeutic research.
由于化疗耐药性，结直肠癌是一项重大的全球健康挑战，因此需要新的治疗方法。葫芦素D具有抗癌特性，显示出了前景，但其对结直肠癌的影响尚未得到充分了解。我们使用MTT法和Annexin V/7-AAD染色，随后通过流式细胞术进行凋亡分析，研究了葫芦素D对结直肠癌细胞系的影响。公共数据库有助于识别葫芦素D和与结直肠癌相关的基因靶点，用于网络药理学分析。使用STRING构建蛋白质-蛋白质相互作用网络，并在Cytoscape中进行分析。使用ClueGo进行基因本体论和KEGG通路富集分析。通过Autodock Vina进行分子对接研究，并在Discovery Studio中进行可视化。蛋白质免疫印迹法评估了葫芦素D作用下关键靶点的蛋白质表达变化。葫芦素D剂量依赖性地降低了结直肠癌细胞活力并诱导凋亡。网络药理学确定了STAT3、AKT1、CCND1和CASP3等关键靶点。分子对接证实了与这些靶点的强相互作用。富集分析突出了其参与“PI3K-AKT”、“JAK-STAT”和“ErbB”信号通路。这些发现表明葫芦素D是一种潜在的抗结直肠癌药物，对细胞活力和凋亡具有显著影响，并涉及关键的癌症相关通路，使其成为进一步结直肠癌治疗研究的有希望的候选药物。
