BACKGROUND: The gastric epithelium is continuously exposed to toxic reactive oxygen species and matrix metalloproteinases (MMPs) are the enzymes known for their roles in the invasion of tumor cells. Here, we report the suppression of matrix metalloproteinase 3 (MMP-3) in gastric cancer cell line AGS by small interfering RNA (siRNA) transfection and its potential role in gastric cancers. METHODS: Oxidative stress in the cell lines was assessed following H2O2 exposure using an oxidative stress marker, 2,7-dichlorofluorescein diacetate (DCFDA). Transfection of cells with small interfering RNA specific to MMP-3, Transwell invasion assay, quantitative reverse transcriptase polymerase chain reaction analysis, and over-expression of MMP-3 were used to determine the potential role of MMP-3 gene in gastric cancers. RESULTS: The silencing of the MMP-3 gene resulted in a decrease of invading AGS while the over-expression of it caused an increase in the invading cells compared to the untreated control cells. Moreover, it also caused a 4.1 fold increase in matrix metalloproteinase 10 (MMP-10) and a 7.4 fold decrease in matrix metalloproteinase 15 (MMP-15) mRNA expression levels. CONCLUSIONS: Our results show that the silencing of the MMP-3 gene decreases the number of invading AGS cells and additionally, affects the expressions of MMP-10 and MMP-15, suggesting that targeting the MMP-3 gene in gastric cancers might be a therapeutic approach due to its effects on the invasion of AGS cells and the expression of the MMP-15 gene.
BACKGROUND: The gastric epithelium is continuously exposed to toxic reactive oxygen species and matrix metalloproteinases (MMPs) are the enzymes known for their roles in the invasion of tumor cells. Here, we report the suppression of matrix metalloproteinase 3 (MMP-3) in gastric cancer cell line AGS by small interfering RNA (siRNA) transfection and its potential role in gastric cancers. METHODS: Oxidative stress in the cell lines was assessed following H2O2 exposure using an oxidative stress marker, 2,7-dichlorofluorescein diacetate (DCFDA). Transfection of cells with small interfering RNA specific to MMP-3, Transwell invasion assay, quantitative reverse transcriptase polymerase chain reaction analysis, and over-expression of MMP-3 were used to determine the potential role of MMP-3 gene in gastric cancers. RESULTS: The silencing of the MMP-3 gene resulted in a decrease of invading AGS while the over-expression of it caused an increase in the invading cells compared to the untreated control cells. Moreover, it also caused a 4.1 fold increase in matrix metalloproteinase 10 (MMP-10) and a 7.4 fold decrease in matrix metalloproteinase 15 (MMP-15) mRNA expression levels. CONCLUSIONS: Our results show that the silencing of the MMP-3 gene decreases the number of invading AGS cells and additionally, affects the expressions of MMP-10 and MMP-15, suggesting that targeting the MMP-3 gene in gastric cancers might be a therapeutic approach due to its effects on the invasion of AGS cells and the expression of the MMP-15 gene.
Authors: Mihaela Chivu-Economescu; Lilia Matei; Laura G Necula; Denisa L Dragu; Coralia Bleotu; Carmen C Diaconu Journal: World J Gastroenterol Date: 2018-05-14 Impact factor: 5.742