Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Cinnamic hydroxamic acid inhibits the proliferation of gastric cancer cells via upregulation of miR 145 expression and down-regulation of P13K/Akt signaling pathway

ShanPing Li, SenMao Hu

Department of General Surgery, Affiliated Renhe Hospital of China Three Gorges University, Yichang, Hubei 443000, China;

For correspondence:- SenMao Hu Email: HoytSerranoxcg@yahoo.com Tel:+8615871569439

Accepted: 22 April 2020 Published: 31 May 2020

Citation: Li S, Hu S. Cinnamic hydroxamic acid inhibits the proliferation of gastric cancer cells via upregulation of miR 145 expression and down-regulation of P13K/Akt signaling pathway. Trop J Pharm Res 2020; 19(5):957-963 doi: 10.4314/tjpr.v19i5.7

© 2020 The authors.
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Abstract

Purpose: To investigate the anti-proliferative effect of cinnamic hydroxamic acid (CHA) on gastric cancer (GC) cells, and its mechanism of action.

Methods: Two GC cell lines (SGC?7901 and MKN1) and normal human gastric epithelial cells (GES1) were used for this study. The GC cells were cultured in Dulbecco’s modified Eagle’s medium (DMEM)supplemented with 10 % fetal bovine serum (FBS) and 1 % penicillin/streptomycin solution at 37 °C for 24 h in a humidified atmosphere of 5 % CO2 and 95 % air. GES1 cells were cultured in RPMI medium supplemented with 10 % FBS only. Cell viability and apoptosis were determined using 3 (4,5 dimethyl thiazol 2 yl) 2,5 diphenyl 2H tetrazolium bromide (MTT), and flow cytometric assays, respectively. The level of expression of microRNA-145 (miR-145) was determined using real-time quantitative polymerase chain reaction (qRT-PCR). Protein expressions of c-Myc, p-AKT, PI3K, p21, and matrix metalloproteinase (MMP)-2 and MMP-9were determined using Western blotting.

Results: Treatment of GC cells with CHA for 72 h led to significant and dose-dependent reduction in their viability, and significant and dose-dependent increase in the number of apoptotic cells (p < 0.05). It also significantly arrested GC cell cycle at G1 phase (p < 0.05). The treatment significantly and dose-dependently decreased SGC?7901 and MKN1 cell migration and invasion, and upregulated miR-145 mRNA expression (p < 0.05). The expression of miR-145 mRNA was significantly higher in MKN1 cells than in SGC?7901cells (p < 0.05). Treatment of SGC?7901 and MKN1 cells with CHA significantly down-regulated protein expressions of c-Myc, MMP-2/9, PI3K and p-AKT, but upregulated p21 protein expression (p< 0.05).

Conclusion: These results show that CHA inhibits the proliferation of GC cells via upregulation of miR-145 expression and down-regulation of P13K/Akt signaling pathway. Therefore, CHA has a good potential as a therapeutic agent for the management of gastric cancer

Keywords: Apoptosis, Cinnamic hydroxamic acid, Gastric cancer, Metastasis, Proliferation