Dihydrocapsaicin secreted by RYK silencing-modified bone marrow-derived mesenchymal stem cells trigger apoptosis of gastric cancer cells

Bone marrow-derived mesenchymal stem cells (BMSCs) have been proven to be recruited into the tumor microenvironment and contribute to gastric cancer (GC) progression, However, the exact mechanisms remain poorly understood. This study explored the potential mechanism of RYK-silenced BMSCs on gastric cancer cell apoptosis. Firstly, BMSCs were transfected with the RYK siRNA and their corresponding negative controls, and cell co-culture were used to explore the interaction between different BMSCs and NCI-N87 cells. Then, Cancer cell cycle apoptosis was evaluated by flow cytometry. Western blot analysis was performed to determine the protein levels of Caspase3, Bax, and Bcl-2 in NCI-N87 cells. Then metabolomics was used to analyze the differential metabolites in different BMSCs. Furthermore, the NCI-N87 cells were treated with dihydrocapsaicin (DHC), and the proliferation activity, apoptosis level, and expression of apoptosis-related proteins in the NCI-N87 cells were detected after different DHC treatments. Compared to NCI-N87 cells cultured alone, co-culture with si-NC-modified BMSCs reduced apoptosis in NCI-N87 cells. However, co-culture with si-RYK-BMSCs significantly increased apoptosis. Additionally, DHC, a metabolic product secreted by BMSCs after RYK interference, suppresses NCI-N87 cell growth, promotes cell death, and increases the expression of apoptosis-related proteins. These findings suggest that RYK silencing-modified BMSCs can induce the apoptosis of NCI-N87 cells, potentially through increased secretion of DHC.