Table1_Network pharmacology and molecular docking reveal the mechanisms of curcumin activity against esophageal squamous cell carcinoma.XLSX

Background: Curcumin (CUR), an effective traditional Chinese medicinal extract, displays good anti-cancer activity against various cancers. Nevertheless, the impacts and fundamental mechanisms of CUR to treat esophageal squamous cell carcinoma (ESCC) yet to be comprehensively clarified. This study examined the suppressive impacts of CUR on ESCC.
Methods: For a comprehensive understanding of the effect of CUR in ESCC. The CUR targets and ESCC-related genes were identified respectively, and the intersection targets between CUR and ESCC were acquired. Then, we examined the intersection targets and discovered genes that were expressed differently in ESCC. Using DAVID, enrichment analyses were conducted on the targets of CUR-ESCC. The STRING database and Cytoscape v.3.9.1 were utilized to build networks for protein-protein interaction (PPI) and drug-target-pathway. Furthermore, the interactions between CUR and its core targets were confirmed by molecular docking studies. To confirm the effects of CUR on ESCC cells, in vitro experiments were finally conducted.
Results: Overall, 47 potential CUR targets for ESCC treatment were identified. The KEGG pathway enrichment analysis identified 61 signaling pathways, primarily associated with the FoxO signaling, the cell cycle, cellular senescence, the IL-17 signaling pathway which play important roles in ESCC progression. In the PPI network and the docking results identified CHEK1 and CDK6 as the core targets that positively associated with ESCC survival. CUR arrested ESCC cells at the G2/M and S phases, as shown by flow cytometry. Colony formation and CCK8 assays showed that CUR can inhibit the proliferative ability of ESCC cells. The Transwell invasion results validated that CUR can significantly inhibit the invasion rates of ESCC cells.
Conclusion: Collectively, these findings indicate that CUR exhibits pharmacological effects on multiple targets and pathways in ESCC.

背景：姜黄素（Curcumin, CUR）作为一种高效的传统中药提取物，对多种癌症均展现出优异的抗癌活性。然而，姜黄素治疗食管鳞状细胞癌（Esophageal Squamous Cell Carcinoma, ESCC）的具体作用及其核心机制仍有待全面阐明。本研究旨在探讨姜黄素对食管鳞状细胞癌的抑制效应。
方法：为全面解析姜黄素在食管鳞状细胞癌中的作用效果，本研究分别筛选鉴定了姜黄素的作用靶点与食管鳞状细胞癌相关基因，并获取二者的交集靶点。随后，对交集靶点进行分析，筛选出食管鳞状细胞癌中差异表达的基因。借助DAVID数据库对姜黄素-食管鳞状细胞癌交集靶点开展富集分析。通过STRING数据库与Cytoscape v.3.9.1软件分别构建蛋白质相互作用（Protein-Protein Interaction, PPI）网络及药物-靶点-通路网络。此外，通过分子对接实验验证姜黄素与其核心靶点之间的结合相互作用。最后，通过体外实验验证姜黄素对食管鳞状细胞癌细胞的生物学效应。
结果：本研究共鉴定得到47个用于食管鳞状细胞癌治疗的潜在姜黄素作用靶点。KEGG通路富集分析共筛选出61条信号通路，主要涉及FoxO信号通路、细胞周期、细胞衰老及IL-17信号通路等与食管鳞状细胞癌进展密切相关的通路。通过PPI网络与分子对接结果筛选得到CHEK1与CDK6作为核心靶点，二者与食管鳞状细胞癌患者的生存预后呈正相关。流式细胞术检测结果显示，姜黄素可将食管鳞状细胞癌细胞阻滞于G2/M期与S期。集落形成实验与CCK8实验结果表明，姜黄素能够抑制食管鳞状细胞癌细胞的增殖能力。Transwell侵袭实验结果证实，姜黄素可显著降低食管鳞状细胞癌细胞的侵袭速率。
结论：综上，本研究结果表明，姜黄素可通过多靶点、多通路发挥抗食管鳞状细胞癌的药理活性。