Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Pyrimidine-thioindole inhibits gastric cancer cell proliferation via up-regulation of expression of tumor suppressor miR-145

Rong Zhang¹, Chunhe Yao²

¹Department of Gastroenterology; ²Department of General Surgery, Xianyang Hospital of Yan'an University, Xianyang, Shaanxi 712000, China.

For correspondence:- Chunhe Yao Email: zhangrzt@126.com Tel:+862933351603

Accepted: 25 October 2020 Published: 30 November 2020

Citation: Zhang R, Yao C. Pyrimidine-thioindole inhibits gastric cancer cell proliferation via up-regulation of expression of tumor suppressor miR-145. Trop J Pharm Res 2020; 19(11):2343-2348 doi: 10.4314/tjpr.v19i11.14

© 2020 The authors.
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Abstract

Purpose: To investigate the effect of pyrimidine-thioindole on gastric cancer proliferation and the underlying mechanism of action.

Methods: Cell viability and apoptosis were determined using MTT assay and Annexin V/PI assay, respectively. Reverse transcription-polymerase chain reaction (RT-PCR) was used for the determination of expression levels of miR-145, while protein expression levels were assayed by western blotting.

Results: Pyrimidine-thioindole treatment significantly inhibited the proliferation of AGS and SNU-5 cells (p < 0.05), but had no effect on the viability of GES-1 cells. Exposure to pyrimidine-thioindole at doses of 8 and 10 µM significantly enhanced the apoptosis of AGS and SNU-5 cells (p < 0.05). Pyrimidine-thioindole exposure markedly increased the proportions of AGS and SNU-5 cells in G1 phase (p < 0.05). In AGS and SNU-5 cell lines, pyrimidine-thioindole exposure at doses of 8 and 10 µM significantly upregulated the expression of miR-145, with higher enhancement of miR-145 expression in AGS cells than in SNU-5 cells. Moreover, pyrimidine-thioindole downregulated the expressions of MMP-2, MMP-9, c-Myc, p-PI3K and p-AKT in AGS and SNU-5 cells. Pyrimidine-thioindole treatment enhanced the expression of p21 in AGS and SNU-5 cells, relative to untreated cells (p < 0.05).

Conclusion: These results suggest that pyrimidine-thioindole activates apoptotic signaling pathway, leading to reduction in cell proliferation and arrest of cell cycle. Moreover, it de-activates PI3K/AKT pathway and promotes miR-145 expression in AGS and SNU-5 cells. Thus, pyrimidine-thioindole has therapeutic significance for the management of gastric cancer.

Keywords: Gastric cancer, Pyrimidine, Indole, Apoptosis, Cell proliferation