Effect of DHPS on Metastasis of Gastric Cancer and its Possible Mechanism / 胃肠病学

ABSTRACT

Background:Deoxyhypusine synthase(DHPS)is a key factor in post-translational modification of the precursor of eukaryotic initiation factor 5A(eIF-5A),and eIF-5A is closely related to the regulation of proliferation and invasion of tumor cells. Aims:To investigate the expression of DHPS in gastric cancer and its clinical significance,and to explore the possible mechanism of its effect on metastasis of gastric cancer. Methods:Tissue microarray containing 92 gastric cancer tissues and paired adjacent cancerous tissues was employed to detect the DHPS expression by using immunohistochemical staining,and the correlation of DHPS expression with the clinicopathological characteristics of gastric cancer was analyzed. DHPS-siRNA and GC7,an inhibitor of DHPS were used,respectively to intervene human gastric cancer cell line MGC803. The invasive ability of MGC803 cells was assessed by cell invasion assay,and the expressions of metastasis-related proteins including vascular endothelial growth factor(VEGF),matrix metalloproteinase 2(MMP2)and MMP9 were detected by ELISA. Results:In 62(67.4%)cases of gastric cancer,DHPS was highly expressed,and its expression was closely related to tumor diameter,TNM stage and depth of invasion(P <0.05),but not related to gender,age,lymph node metastasis and distant metastasis(P >0. 05). Both DHPS-siRNA and GC7 could down-regulate the invasiveness of MGC803 cells,while the former could also reduce the expressions of VEGF,MMP2 and MMP9 proteins(P <0.05). Conclusions:DHPS is highly expressed in gastric cancer and associated with tumor invasion and progression. DHPS is expected to be a new target for diagnosis and treatment of gastric cancer because of its regulatory effect on invasion and metastasis of tumor cells.