DHPS在胃癌转移中的作用及其机制研究  

Effect of DHPS on Metastasis of Gastric Cancer and its Possible Mechanism

作　　者：苏文雨[1] 王吉林[1] 熊华[1] 房静远[1] 

机构地区：[1]上海交通大学医学院附属仁济医院消化内科,上海市消化疾病研究所,200001

出　　处：《胃肠病学》2018年第2期70-74,共5页Chinese Journal of Gastroenterology

基　　金：国家自然科学基金青年科学基金项目(81302090);上海市自然科学基金青年项目(13ZR1457200)

摘　　要：背景:脱氧羧腐胺赖氨酸合酶(DHPS)是催化真核生物翻译起始因子5A(e IF-5A)前体翻译后修饰的关键因子,而后者与肿瘤细胞增殖、侵袭的调控密切相关。目的:探讨DHPS在胃癌中的表达及其临床意义,探究其在胃癌转移中的可能作用机制。方法:使用含92例胃癌组织及其相应癌旁组织的组织芯片,以免疫组化染色检测DHPS表达,分析其表达与胃癌临床病理特征间的关联。利用DHPS-siRNA和DHPS抑制剂GC7分别干预人胃癌细胞株MGC803,以细胞侵袭实验检测细胞侵袭力,以ELISA法检测转移相关蛋白血管内皮生长因子(VEGF)、基质金属蛋白酶2(MMP2)、MMP9表达。结果:62例(67.4%)胃癌组织DHPS高表达,其表达强度与肿瘤直径、TNM分期、浸润深度密切相关(P<0.05),与患者性别、年龄、淋巴结转移和远处转移无明显相关性(P>0.05)。DHPSsiRNA和GC7均可显著下调MGC803细胞的侵袭力,前者还可下调VEGF、MMP2和MMP9蛋白表达(P<0.05)。结论:DHPS在胃癌中表达升高,并与肿瘤浸润和进展密切相关。其参与胃癌细胞侵袭和转移的调控,有望成为胃癌诊断和治疗的新靶点。Background: Deoxyhypusine synthase( DHPS) is a key factor in post-translational modification of the precursor of eukaryotic initiation factor 5 A( e IF-5 A),and e IF-5 A 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.

关 键 词：胃肿瘤 肿瘤转移 脱氧羧腐胺赖氨酸合酶 真核生物翻译起始因子5A 基因表达调控 

分 类 号：R735.2[医药卫生—肿瘤]