Cancer medicine
Cyclopiane Suppresses Gastric Cancer Invasion and Angiogenesis via the CYR61/αvβ3 Integrin/NF-κB Pathway
By Zhang Y, Tian H, Wang S and 5 others.
Abstract
Background
Cysteine-rich angiogenic inducer 61 (CYR61), a matricellular protein, has been implicated in gastric cancer aggressiveness through activation of integrin-mediated NF-κB signaling; however, effective pharmacological strategies targeting this axis remain limited. Cyclopiane, a bioactive small-molecule compound, has shown potential anti-tumor activity, but its role and underlying mechanisms in gastric cancer have not been fully elucidated. This study aimed to investigate whether Cyclopiane suppresses gastric cancer invasion and angiogenesis via modulation of the CYR61/αvβ3 integrin/NF-κB signaling pathway.
Methods
Human gastric cancer cell lines AGS and MKN45 were treated with increasing concentrations of Cyclopiane. Cell viability was assessed using MTT assays, while invasive capacity was evaluated using Matrigel-coated Transwell assays. TUNEL staining was used to assess changes in apoptosis in tumor cells. The expression of invasion-, angiogenesis-, and inflammation-related proteins was analyzed by Western blot (WB) and enzyme-linked immunosorbent assay (ELISA). Transcriptomic profiling of AGS cells treated with Cyclopiane versus vehicle control was performed to identify differentially expressed genes and enriched signaling pathways. CYR61 overexpression was achieved via adeno-associated virus (AAV-CYR61), with its pathway involvement further validated using integrin αvβ3 antagonists. The conventional anticancer drug 5-fluorouracil (5-FU) was employed to compare Cyclopiane's therapeutic effects. In vivo experiments utilized a nude mouse xenograft model to evaluate changes in tumor growth, angiogenesis, and inflammatory responses following Cyclopiane treatment.