【摘 要】
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Objective:To investigate the inhibitory effects of paeoniflorin on migration-and invasionpromoting capacities of gastric cancer associated fibroblasts (GCAFs) and to explore the molecular mechanism underlying the effects.Methods:Paired gastric normal fibr
【机 构】
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The Laboratory for Tumor Molecular Diagnosis, Affiliated People’s Hospital of Inner Mongolia Medical
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Objective:To investigate the inhibitory effects of paeoniflorin on migration-and invasionpromoting capacities of gastric cancer associated fibroblasts (GCAFs) and to explore the molecular mechanism underlying the effects.Methods:Paired gastric normal fibroblast (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 enzymelinked 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＜0.05).GCAFs produced and secreted more IL-6 into the conditioned medium than GNFs,leading to over-activation of STAT3-MMP signaling in AGS cells.Paeoniflorin suppressed IL-6 production and secretion by up-regulating microRNA149 expression in GCAFs,and subsequently prevented GCAFs from activating IL-6-STAT3-MMP signaling of AGS cells.Conclusions:Paeoniflorin inhibits the migration-and invasion-promoting capacities of GCAFs by targeting microRNA-149 and IL-6.Paeoniflorin is potentially a novel therapeutic agent against cancer microenvironment.
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