The Therapeutic Effect of Melatonin on GC by Inducing Cell Apoptosis and Autophagy Induced by Endoplasmic Reticulum Stress

摘要: Background Gastric cancer (GC) is the main malignancy affecting a large population worldwide. Lack of effective enough treatment one leading factors contributing to high mortality rate. Melatonin, naturally occurring compound, has been proven exert cytotoxic and antiproliferative effects on human gastric cancers. Nevertheless, mechanisms anti-gastric melatonin remain elucidated. It believed that endoplasmic reticulum (ER) stress its resultant unfolded protein response (UPR) are connected survival, progression, chemoresistance various tumor cells via multiple cellular procedures, such as autophagy. In this study, cell lines AGS SGC-7901 was assessed reveal interaction between melatonin, stress, autophagy in cancer. Methods CCK-8, wound healing analysis, colony formation assay, immunofluorescence Western blotting, flow cytometry, animal models were used current study. Results The data demonstrated could inhibit GC growth, proliferation, invasion both vivo vitro. Apoptosis induced concentration-dependent manner melatonin-induced ER stress. Melatonin expression apoptotic autophagy-related proteins, which markedly attenuated by inhibitor 4-PBA 3-MA. addition, we specific IRE1 STF 083010, finding inhibiting considerably relieve stress-induced activity, revealed reduction LC3-II Beclin-1. Conclusion This study confirmed inhibition proliferation mediated activation IRE/JNK/Beclin1 signaling.