文献类型： 外文期刊

作者： Xu, Xiaoqing ¹ ; Yu, Yaping ¹ ; Yang, Li ² ; Wang, Bingshu ¹ ; Fan, Yonghao ¹ ; Ruan, Banzhan ¹ ; Zhang, Xiaodian ¹ ; Dai, Haofu ² ; Mei, Wenli ² ; Jie, Wei ¹ ; Zheng, Shaojiang ¹ ;

作者机构： 1.Hainan Med Univ, Affiliated Hosp & Canc Inst 1, Dept Oncol, Haikou, Peoples R China

2.Chinese Acad Trop Agr Sci, Inst Trop Biosci & Biotechnol, Key Lab Nat Prod Res & Dev Li Folk Med Hainan Prov, Haikou, Peoples R China

3.Hainan Med Univ, Childrens Med Ctr, Key Lab Emergency, Key Lab Trop Cardiovasc Dis Res Hainan Prov & Hain, Haikou, Peoples R China

4.Hainan Med Univ, Key Lab Emergency & Trauma, Minist Educ, Haikou, Peoples R China

5.Hainan Med Univ, Key Lab Trop Cardiovasc Dis Res Hainan Prov, Haikou, Peoples R China

6.Hainan Med Univ, Hainan Women & Childrens Med Ctr, Haikou, Peoples R China

关键词： pancreatic ductal adenocarcinoma; Dendrobium nobile; Dendrobin A; network pharmacology; bioinformatics; PLAU

期刊名称：FRONTIERS IN PHARMACOLOGY （ 影响因子：5.6； 五年影响因子：6.1 ）

ISSN：

年卷期： 2023 年 14 卷

页码：

收录情况： SCI

摘要： Background: Dendrobium nobile (D. nobile), 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 in vitro experiments to explore the effect and mechanism of Dendrobin A, the active ingredient of D. nobile, against pancreatic ductal adenocarcinoma (PDAC).Methods: 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, in vitro 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.Results: 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. In vitro 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.Conclusion: Dendrobin A, a representative active ingredient of D. nobile, can effectively fight against PDAC by targeting PLAU. Our results provide the foundation for future PDAC treatment based on D. nobile.