Inhibition of lysyl oxidase expression by dextran sulfate affects invasion and migration of gastric cancer cells.

ABSTRACT

In the present study, the effect of dextran sulfate (DS) on the metastasis and invasion of human gastric cancer cells and its key underlying mechanism were investigated. The levels of hypoxia­inducible factor 1α (HIF­1α), transforming growth factor ß (TGF­ß) and lysyl oxidase (LOX) expression were evaluated in human gastric cancer and peritumoral tissues by immunohistochemical analysis. Cell proliferation and apoptosis were also examined using the Cell Counting Kit­8 assay and flow cytometry. The effect of DS on the invasion and migration of BGC­823 cells was assessed using a Transwell assay. BGC­823 cells were divided into the control (phosphate­buffered saline­treated) and experimental (DS­treated) groups, and cultured for different times under hypoxic conditions. Subsequently, LOX and TGF­ß expression levels in the cells were measured by immunocytochemistry, immunofluorescence, reverse transcription­quantitative polymerase chain reaction and western blot analysis. HIF­1α, TGF­ß and LOX expression levels were significantly higher in human gastric cancer tissues as compared with that in adjacent tissues. DS influenced cell proliferation and apoptosis in a dose­dependent manner. Furthermore, DS reduced the number of invaded and migrated cells. Under hypoxic conditions, DS reduced HIF­1α, TGF­ß and LOX expression levels in BGC­823 cells. After 12 h, the effect of combination of DS and ß­aminopropionitrile (BAPN) on LOX and TGF­ß protein levels was more significant compared with that of DS or BAPN alone. Therefore, DS may inhibit the invasion and migration of human gastric cancer cells under hypoxic conditions by influencing LOX.