Mechanisms of Zanthoxyli Pericarpium-Zingiberis Rhizoma in the Treatment of Gastric Cancer Based on Network Pharmacology and Experimental Validation

Qian Gu,1 Shuai Duan,1 Joanna Japhet Tibenda,1 Boyun Gou,1 Shicong Huang,1 Guoqing Chen,1 Na Ning,1 Yuhua Du,1 Wenjing Liu,2 Yi Nan,2,* Ling Yuan1,* 1College of Pharmacy, Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 2Key Laboratory of Ningxia Ethnomedicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi Nan, Key Laboratory of Ningxia Ethnomedicine Modernization, Ministry of Education, Ningxia Medical University, 1160 Shengli Street, Xingqing District, Yinchuan, Ningxia, 750004, People’s Republic of China, Email [email protected] Ling Yuan, College of Pharmacy, Ningxia Medical University, 1160 Shengli Street, Xingqing District, Yinchuan, Ningxia, 750004, People’s Republic of China, Email [email protected]: Malignant tumors, as a major challenge in global public health, have posed a significant threat to human life and health. Although traditional chemotherapy can inhibit tumor growth, it is often associated with serious adverse effects and tolerance. Against this background, Chinese medicine therapies have gradually gained wide recognition, and they play an important role in the treatment of gastric cancer (GC). As the core combination of the traditional prescription “Dajianzhong Tang”, the medicinal pair of Zanthoxyli Pericarpium and Zingiberis Rhizoma (ZP-ZR) has shown unique advantages in tumor treatment.Purpose: To explore the mechanism of action of ZP-ZR in the treatment of GC using network pharmacology, bioinformatics analysis and in vitro experimental validation, and to provide a theoretical basis for subsequent experimental studies.Patients and Methods: Subsequently, the effects of ZP-ZR on the proliferative ability of gastric cancer HGC-27 and AGS cell lines were verified by CCK-8, apoptosis, cycle and colony formation assays. The effects of ZP-ZR on the metastatic ability of GC cells were evaluated by Wound healing, transwell cell invasion and transwell cell migration assays. In addition, we evaluated the expression of Hub genes, pathway proteins and mRNAs by Western blot and qRT-PCR.Results: ZP-ZR mainly regulated EGFR, PTGS2, MMP9, CXCL8, BCL2L1, CDK6, KIT target genes and PI3K/Akt pathway in GC for the treatment of gastric cancer. ZP-ZR inhibited the proliferation, induced apoptosis, blocked the cell cycle, and inhibited cell migration and invasion in AGS and HGC-27 cell lines. In addition, ZP-ZR affected the expression of PI3K-Akt-related proteins and decreased the mRNA expression of Hub genes.Conclusion: ZP-ZR treats GC through the PI3K-Akt pathway.The present study provides a new idea for further investigation of ZP-ZR in the treatment of GC.Keywords: zanthoxyli pericarpium-zingiberis rhizoma, gastric cancer, network pharmacology, molecular mechanism, in vitro experimental validation