Xu Xiaoqing, Yu Yaping, Yang Li, Wang Bingshu, Fan Yonghao, Ruan Banzhan, Zhang Xiaodian, Dai Haofu, Mei Wenli, Jie Wei, Zheng Shaojiang
Department of Oncology of the First Affiliated Hospital & Cancer Institute, Hainan Medical University, Haikou, China.
Key Laboratory of Natural Products Research and Development from Li Folk Medicine of Hainan Province, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou, China.
Front Pharmacol. 2023 Mar 1;14:1079539. doi: 10.3389/fphar.2023.1079539. eCollection 2023.
(), a traditional Chinese medicine, has received attention as an anti-tumor drug, but its mechanism is still unclear. In this study, we applied network pharmacology, bioinformatics, and experiments to explore the effect and mechanism of Dendrobin A, the active ingredient of , against pancreatic ductal adenocarcinoma (PDAC). The databases of SwissTargetPrediction and PharmMapper were used to obtain the potential targets of Dendrobin A, and the differentially expressed genes (DEGs) between PDAC and normal pancreatic tissues were obtained from The Cancer Genome Atlas and Genotype-Tissue Expression databases. The protein-protein interaction (PPI) network for Dendrobin A anti-PDAC targets was constructed based on the STRING database. Molecular docking was used to assess Dendrobin A anti-PDAC targets. PLAU, one of the key targets of Dendrobin A anti-PDAC, was immunohistochemically stained in clinical tissue arrays. Finally, experiments were used to validate the effects of Dendrobin A on PLAU expression and the proliferation, apoptosis, cell cycle, migration, and invasion of PDAC cells. A total of 90 genes for Dendrobin A anti-PDAC were screened, and a PPI network for Dendrobin A anti-PDAC targets was constructed. Notably, a scale-free module with 19 genes in the PPI indicated that the PPI is highly credible. Among these 19 genes, PLAU was positively correlated with the cachexia status while negatively correlated with the overall survival of PDAC patients. Through molecular docking, Dendrobin A was found to bind to PLAU, and the Dendrobin A treatment led to an attenuated PLAU expression in PDAC cells. Based on clinical tissue arrays, PLAU protein was highly expressed in PDAC cells compared to normal controls, and PLAU protein levels were associated with the differentiation and lymph node metastatic status of PDAC. experiments further showed that Dendrobin A treatment significantly inhibited the proliferation, migration, and invasion, inducing apoptosis and arresting the cell cycle of PDAC cells at the G2/M phase. Dendrobin A, a representative active ingredient of , can effectively fight against PDAC by targeting PLAU. Our results provide the foundation for future PDAC treatment based on .
（某中药名称，原文未给出具体中文名称）作为一种抗肿瘤药物受到了关注，但其作用机制仍不清楚。在本研究中，我们应用网络药理学、生物信息学和实验来探索（某中药名称）的活性成分石斛碱A对胰腺导管腺癌（PDAC）的作用及机制。利用SwissTargetPrediction和PharmMapper数据库获取石斛碱A的潜在靶点，并从癌症基因组图谱（The Cancer Genome Atlas）和基因型-组织表达（Genotype-Tissue Expression）数据库中获得PDAC与正常胰腺组织之间的差异表达基因（DEGs）。基于STRING数据库构建石斛碱A抗PDAC靶点的蛋白质-蛋白质相互作用（PPI）网络。采用分子对接评估石斛碱A抗PDAC靶点。对石斛碱A抗PDAC的关键靶点之一PLAU在临床组织芯片上进行免疫组化染色。最后，通过实验验证石斛碱A对PLAU表达以及PDAC细胞增殖、凋亡、细胞周期、迁移和侵袭的影响。共筛选出90个石斛碱A抗PDAC的基因，并构建了石斛碱A抗PDAC靶点的PPI网络。值得注意的是，PPI中一个包含19个基因的无标度模块表明该PPI具有高度可信度。在这19个基因中，PLAU与恶病质状态呈正相关，而与PDAC患者的总生存期呈负相关。通过分子对接发现，石斛碱A与PLAU结合，且石斛碱A处理导致PDAC细胞中PLAU表达减弱。基于临床组织芯片，与正常对照相比，PLAU蛋白在PDAC细胞中高表达，且PLAU蛋白水平与PDAC的分化和淋巴结转移状态相关。实验进一步表明，石斛碱A处理显著抑制PDAC细胞的增殖、迁移和侵袭，诱导细胞凋亡并使PDAC细胞的细胞周期停滞在G2/M期。石斛碱A作为（某中药名称）的代表性活性成分，可通过靶向PLAU有效对抗PDAC。我们的研究结果为未来基于（某中药名称）的PDAC治疗提供了依据。
