Melatonin Inhibit the Angiogenesis of Gastric Cancer by Nuclear Receptor

Abstract

This study aims to explore the relationship between melatonin (MLT) and gastric cancer angiogenesis by nuclear receptor with ELISA, real‐time quantitative RT‐PCR, IHC, Western blot, and siRNA methods.1. The anti‐angiogenic function of MLT on the human gastric cancer cells and the impact on MLT nuclear receptor in vitro. MLT was time‐dependent in inhibiting proliferation of human gastric cancer cell lines MGC‐803, SGC‐7901, and AGS; Chemical hypoxia simulated by 100uM CoCl2 increased proliferation of SGC‐7901 cells; MLT decreased the expression of VEGF mRNA and protein of SGC‐7901; MLT decreased the expression of nuclear receptor RZR/RORγ mRNA and protein of SGC‐7901.2. The anti‐angiogenic mechanism of MLT on human gastric cancer cells SGC‐7901 in vitro and the targets of MLT nuclear receptor RZR/RORγ. The RZR/RORγ silent by siRNA antagonized significantly MLT's inhibition on gastric cancer cell proliferation.After the 24h intervention by 3mM MLT, the mRNA and protein expression of RZR / RORγ,SENP1,HIF‐1α and VEGF was significantly decreased; but the expression of SENP1, HIF‐1α, VEGF mRNA and protein was increased.3. The anti‐angiogenic mechanism of MLT on the gastric cancer in vivo with nude mice.We established the tumor‐bearing nude mice model of gastric cancer SGC‐7901 with intervention by different concentrations of MLT. MLT reduced the tumor volume and weight of the gastric cancer; MLT inhibited tumor proliferation and angiogenesis by decreasing the expression of RZR / RORγ ,SENP1 ,HIF‐1α, VEGF and MVD.The present study confirmed that MLT is able to inhibit gastric cancer angiogenesis both in vivo and in vitro. It's major mechanism is reducing the expression of nuclear receptor RZR/RORγ and decreasing the expression of SENP1,HIF‐ 1α,VEGF.