Paeoniflorin Inhibits Migration- and Invasion-Promoting Capacities of Gastric Cancer Associated Fibroblasts

Objective To investigate the inhibitory effects of paeoniflorin on migration- and invasion-promoting capacities of gastric cancer associated fibroblasts (GCAFs) and to explore the molecular mechanism underlying the effects. Methods Paired gastric normal fifbroblast (GNF) and GCAF cultures were established from resected tissues. GCAFs were treated with control medium, or 2.5, 5 or 10 μg/mL paeoniflorin. Conditioned media were prepared from GNFs, GCAFs, control-treated GCAFs and paeoniflorin-treated GCAFs, and used to culture AGS human gastric cancer cells. The migration and invasion capacities of AGS cells were determined with wound healing test and transwell invasion assay, respectively. The interleukin 6 (IL-6) mRNA and microRNA-149 expression in GCAFs were detected by reverse transcription-quantitative polymerase chain reaction. The IL-6 protein expression and secretion by GCAFs were measured with Western blot and enzyme-linked immunosorbent assay analysis, respectively. The protein levels of phosphorylated signal transducer and activator of transcription 3 (STAT3), matrix metalloproteinase (MMP) and MMP9 in AGS cells were examined by Western blot. Results GCAFs displayed enhanced capacities to induce AGS cell migration and invasion as compared with GNFs. Paeoniflorin treatment significantly inhibited the migration- and invasion-promoting capacities of GCAFs ( P