Inhibition of the peritoneal metastasis of human gastric cancer cells by dextran sulphate in vivo and in vitro

葡聚糖硫酸酯在体内外对人胃癌细胞腹膜转移的抑制作用

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作者:Yuanyi Xu,Yunning Huang,Honghong Wang,Yong Liu

Abstract

The present study investigated the inhibitory effects of dextran sulphate (DS) on the peritoneal metastasis of gastric cancer by observing the adhesion and implantation of human gastric cancer cells in the omenta of nude mice. DS or PBS was added to the culture medium of gastric cancer MKN1 cells. The adhesion of the cancer cells to the culture dishes, and the morphological changes of fixed and living cancer cells were observed using fluorescence staining and confocal microscopy. In addition, the expression of integrin β1 was measured using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). Gastric cancer BGC-823 cells were peritoneally injected into nude mice to develop an animal model. DS and PBS were peritoneally injected into the experimental and control groups, respectively, concurrently with the tumour cells. Haematoxylin and eosin staining was performed, and the number of carcinoma nodules with celiac implantation was counted. Integrin expression was determined by immunohistochemistry and RT-PCR. The results showed that MKN1 cells strongly expressed integrin β1 in the cell membrane and clustered in vitro. DS inhibited the expression of integrin β1 and reduced cluster formation. In addition, the number of pseudopodia formed by the cells decreased, and the cells maintained a rounded shape. The expression of integrin β1 in the adherent and free cells in the experimental group was reduced to 74 and 38% of the levels in the control group, respectively. In the in vivo study, significantly fewer tumour nodules were observed in the experimental group than in the control group (P<0.01). Integrin β1 expression in the experimental group was decreased significantly compared with that in the control group (P<0.01). The present study indicates that DS inhibits the adhesion of human gastric cancer cells, accompanied by a decrease in the expression of integrin β1. DS may inhibit the metastatic celiac implantation of human gastric cancer cells by downregulating integrin β1.

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