The Study About Msenchymal Stem Cells Pretreated By Resveratrol Inhibited Migration Of Gastric Cancer Cells

Objective: To investigate the role of resveratrol in the Wnt/β-catenin pathway and the expression of cytokines of msenchymal stem cells which derived from gastric cancer tissues(GC-MSCs) and adjacent non-cancerous tissues(GCNMSCs), and explore the effect of the supernatant from GC-MSCs and GCN-MSCs both pretreated by resveratrol on the migration ability of gastric cancer cell line(MGC-803). Then its mechanism was analyzed preliminarily.Methods: Collected the total RNA and supernatant of GC-MSC and GCNMSC both treated with resveratrol directly, qPCR or ELISA was uesd to explore the effect of resveratrol on cytokines(IL-6, VEGF, Wnt) of GC-MSC and GCNMSC; Collected the supernatant of GC-MSC and GCN-MSC pretreated by resveratrol(without resveratrol), luciferase reporter assay was used to detect the change of Wnt/β-catenin pathway of GC-MSC and GCN-MSC, ELISA was applied to measure the content of IL-6 in RES-GC-MSC-CM and RES-GCNMSC-CM; RES-GC-MSC-CM and RES-GCN-MSC-CM acted on MGC-803, cell migration was measured by Transwell migration assay, the expression of epithelial to mesenchymal transition(EMT) associated proteins(E-cadherin, Vimetin),phosphorylated STAT3(p-STAT3) and Wnt/β-catenin signaling pathway related proteins(β-catenin, CD44, CyclinD3) were detected by western blot or immunofluorescence.Results:(1) Resveratrol both reduced the expression of IL-6 and VEGF on mRNA levels of GC-MSC and GCN-MSC when it acted on them directly, with decreased secretion of IL-6 in their supernatant;(2) Resveratrol could inhibit the expression of mRNA of Wnt of GC-MSC and GCN-MSC partly, and antagonize Wnt/β-catenin signaling of GC-MSCs and GCN-MSC;(3) RES-GC-MSC-CM and RES-GCN-MSC-CM could both weaken the migration ability and inhibit the expression of Vimetin of MGC-803, with elevated expression of E-cadherin;(4)RES-GC-MSC-CM could inhibit the expression of Wnt/β-catenin signaling pathway related proteins(β-catenin, CD44, CyclinD3) of MGC-803, with no effect on the expression of p-STAT3;(5) RES-GCN-MSC-CM had no effect on the expression of Wnt/β-catenin signaling pathway related proteins(β-catenin, CD44,CyclinD3) and p-STAT3 of MGC-803.Conclusions: Resveratrol could both reduce the secretion of IL-6 of GC-MSC and GCN-MSC, with decreased expression of IL-6 and VEGF on mRNA levels;RES-GC-MSC-CM and RES-GCN-MSC-CM could weaken the migration ability of MGC-803 by putting off the progress of epithelial-mesenchymal transition;Moreover, Wnt/β-catenin signaling may play an important role in the inhibition of migration ability of MGC-803 by RES-GC-MSC-CM. Resveratrol could inhibit migration ability of gastric cancer cell by targeting to mesenchymal stem cells, it may provide a new insight about the mechanism of resvertrol’s anti-tumor effect.