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Celastrus orbiculatus extract suppresses the epithelial-mesenchymal transition by mediating cytoskeleton rearrangement via inhibition of the Cofilin 1 signaling pathway in human gastric cancer

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Celastrus orbiculatus is a traditional medicinal plant used in the anti-inflammatory and analgesic treatment of various diseases. A previous study demonstrated that ethyl acetate extract of C. orbiculatus (COE) exhibited… Click to show full abstract

Celastrus orbiculatus is a traditional medicinal plant used in the anti-inflammatory and analgesic treatment of various diseases. A previous study demonstrated that ethyl acetate extract of C. orbiculatus (COE) exhibited significant antitumor effects. However, studies concerning the effects and mechanism of COE in terms of suppressing the epithelial-mesenchymal transition (EMT) in human gastric adenocarcinoma cells have not been performed at present. The present study hypothesized that COE may inhibit EMT in gastric adenocarcinoma cells by regulating cell cytoskeleton rearrangement. The effect of COE on the viability of AGS cells was detected by MTT assay. An EMT model was induced by transforming growth factor-β1. Cell cytoskeleton staining, laser scanning confocal microscopy and electronic microscopy were used to detect the changes in cell morphology and microstructure of gastric adenocarcinoma cells prior and subsequent to COE treatment. Invasion and migration assays were used to observe the effect of COE on the metastatic ability of AGS cells in vitro. The effect of COE on the expression of Cofilin 1 and EMT biomarkers, including Epithelial-cadherin, Neural-cadherin, Vimentin and matrix metalloproteinases, was examined by western blotting in AGS cells. The correlation between Cofilin 1 and EMT was investigated with immunofluorescence and cytoskeleton staining methods. The results demonstrated that COE may significantly inhibit the process of EMT in AGS cells, and that this was concentration-dependent. In addition, COE significantly downregulated the level of Cofilin 1 in a concentration-dependent manner. In conclusion, these results suggested that Cofilin 1 was directly involved in the process of EMT in AGS cells, and that it served an important function. COE may significantly inhibit EMT in AGS cells, potentially by inhibiting the activation of the Cofilin 1 signaling pathway. The present study may provide a basis for the development of novel anticancer drugs and the development of novel therapeutic strategies, targeting Cofilin 1 protein.

Keywords: celastrus orbiculatus; emt; microscopy; coe; cofilin; ags cells

Journal Title: Oncology Letters
Year Published: 2017

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