Affiliation:
1. Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Zhejiang, China
2. Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Zhejiang, China
Abstract
Background
Pancreatic cancer is a highly aggressive and fatal disease with limited treatment options and poor prognosis for patients. This study aimed to investigate the impact of XYA-2 {N-(3,7-dimethyl-2,6-octadienyl)-2-aza-2-deoxychaetoviridin A}, a nitrogenated azaphilon previously reported from a deep-sea-derived fungus on the progression of pancreatic cancer cells.
Methods
The inhibitory effects of XYA-2 on cell proliferation, clonogenic potential, cell cycle progression, apoptosis, migration, and invasion were assessed using various assays. The CCK-8 assay, clone formation assay, flow cytometry assay, wound healing assay, and transwell assay were employed to evaluate cell proliferation, clonogenic potential, cell cycle progression, apoptosis, migration, and invasion, respectively. Moreover, we employed RNA-seq and bioinformatics analyses to uncover the underlying mechanism by which XYA-2 influences pancreatic cancer cells. The revealed mechanism was subsequently validated through qRT-PCR.
Results
Our results demonstrated that XYA-2 dose-dependently inhibited the proliferation of pancreatic cancer cells and induced cell cycle arrest and apoptosis. Additionally, XYA-2 exerted a significant inhibitory effect on the invasion and migration of cancer cells. Moreover, XYA-2 was found to regulate the expression of genes involved in multiple cancer-related pathways based on our RNA-seq and bioinformatics analysis.
Conclusion
These findings highlight the potential of XYA-2 as a promising therapeutic option for the treatment of pancreatic cancer.
Funder
Traditional Chinese Medicine Science and Technology Program of Zhejiang Province
Prevention, Diagnosis, and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province
Subject
General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience