Melatonin indirectly decreases gastric cancer cell proliferation and invasion via effects on cancer-associated fibroblasts

Aims: Gastric cancer is a malignant tumor with a poor prognosis, and the interaction between tumor cells and cancer-associated fibroblasts (CAFs) further contributes to progression and treatment failure. Recent studies have revealed the potential value of melatonin in cancer therapy, but its role in gastric cancer and CAFs requires further exploration. Main methods: CAFs were isolated using the tissue block method. Cell Counting Kit-8 and cell cycle assays were used to determine the cell proliferation ability, while the cell metastatic capacity was detected by a wound healing assay and Transwell migration/invasion assay. Furthermore, the expression levels of proteins involved were examined using quantitative real-time PCR (qRT-PCR) and western blotting. Key findings: Melatonin not only inhibits cell proliferation and metastasis by reducing the production of reactive oxygen species (ROS) in gastric cancer cells but also inhibits CAFs-induced gastric cancer cell progression by reducing the production of metalloproteinase 2 (MMP2) and metalloproteinase 2 (MMP9) in CAFs. The direct and indirect inhibitory effects of melatonin on gastric cancer cells are involved in the NF-kB signaling pathways. Significance: This study provides insights into the role of melatonin in the tumor microenvironment, further deepens available knowledge regarding the mechanism of action of melatonin in gastric cancer and suggests the potential value of melatonin in gastric cancer treatment.