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

• Published in: World journal of gastroenterology : WJG 2015-06, Vol.21 (23), p.7197-7207
• Main Authors: Zheng, Yong-Bin, Xiao, Gao-Chun, Tong, Shi-Lun, Ding, Yu, Wang, Qiu-Shuang, Li, Sheng-Bo, Hao, Zhi-Nan
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis - drug effects; Basic Study; Blotting, Western; Carcinoma - drug therapy; Carcinoma - enzymology; Carcinoma - genetics; Carcinoma - pathology; Caspase 3 - metabolism; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic; Glucosides - pharmacology; Humans; MicroRNAs - metabolism; Monoterpenes - pharmacology; Phosphatidylinositol 3-Kinase - metabolism; Phosphorylation; Proto-Oncogene Proteins c-akt - metabolism; Real-Time Polymerase Chain Reaction; Signal Transduction - drug effects; STAT3 Transcription Factor - metabolism; Stomach Neoplasms - drug therapy; Stomach Neoplasms - enzymology; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology; Time Factors; Transfection; Up-Regulation
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v21.i23.7197

To examine the potential anti-tumor activity of paeoniflorin in the human gastric carcinoma cell line MGC-803. 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. 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. In summary, the in vitro data suggest that paeoniflorin is a potential novel therapeutic agent against gastric carcinoma, which inhibits cell viability and induces apoptosis through the up-regulation of miR-124 and suppression of PI3K/Akt and STAT3 signaling.