Paeoniflorin inhibits human gastric carcinoma cell proliferation through up-regulation of microRNA-124 and suppression of PI3K/Akt and STAT3 signaling

AIM: To examine the potential anti-tumor activity of paeoniflorin in the human gastric carcinoma cell line MGC-803. METHODS:Cell viability and cytotoxic effects in MGC-803 cells were analyzed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assay, respectively.Cell apoptosis of MGC-803 cells was measured using flow cytometry, DAPI staining assay and caspase-3 activity assay.Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the expression of microRNA-124 (miR-124) in response to paeoniflorin.The expression of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), phospho-Akt (p-Akt) and phospho-signal transducer and activator of transcription 3 (p-STAT3) were also measured by quantitative RT-PCR and Western blot analysis in normal, miR-124 and anti-miR-124 over-expressing MGC-803 cells, treated with paeoniflorin. RESULTS:Paeoniflorin was found to inhibit MGC-803 cell viability in a dose-dependent manner.Paeoniflorin treatment was associated with the induction of apoptosis and caspase-3 activity in MGC-803 cells.Paeoniflorin treatment significantly increased miR-124 levels and inhibited the expression of PI3K, Akt, p-Akt and p-STAT3 in MGC-803 cells.Interestingly, the over-expression of miR-124 inhibits PI3K/Akt and phospho-STAT3 expressions in MGC-803 cells.PI3K agonist (IGF-1, 1 μg/10 μL) or over-expression of STAT3 reversed the effect of paeoniflorin on the proliferation of MGC-803 cells.Over-expression of anti-miR-124 in MGC-803 cells reversed paeoniflorin-induced up-regulation.