The 5,7,2, 5 -tetrahydroxy-8,6 –dimethoxyflavone up-regulates miR 145 expression and inhibits proliferation of gastric cancer cells

Abstract

IntroductionGastric cancer is a frequently detected malignancy and its incidence has increased over the past decades in East Asia. The present study investigated the effect of 5,7,2, 5 -tetrahydroxy-8,6 –dimethoxyflavone (THDMF) on gastric cancer cells and explored the underlying mechanism.Material and methodsMTT colorimetric assay was used for measurement of MKN28, MKN45and GES 1cell proliferation and flow cytometry for detection of apoptosis. Transwell and wound healing assays were used to observe the invasion and migration abilities of MKN28 cells. The expression of p21, MMP2/-9, PI3K and c Myc proteins was detected by western blotting.ResultsThe THDMF treatment significantly (P<0.05) reduced MKN28 and MKN45 cell proliferation without changing GES 1 cell viability. A significant increase in apoptotic cell population on treatment with THDMF was observed. Treatment of MKN28 cells with THDMF increased percentage of cells in G1 phase. Exposure of MKN28 cells to THDMF caused a marked decrease in invasion and migration potential. The expression of miR 145 was markedly increased in MKN28 cells on treatment with THDMF. In MKN28 cells expression of c Myc, PI3K, p AKT, MMP-2 and MMP-9 was suppressed markedly. The expression of p21 protein was markedly promoted on exposure to THDMF.ConclusionsIn summary, THDMF exhibits anti-cancer effect on gastric cancer cells in vitro by activation of cell apoptosis and arrest of cell cycle. In addition, THDMF promoted miR 145 expression and down-regulation of PI3K/AKT signaling pathway in MKN28 cells. Therefore, THDMF may be utilized as a potential novel therapeutic agent for the treatment of gastric cancer.