果糖代谢相关蛋白GLUT5和KHK在肺腺癌中的表达及其生物学功能  

Expression of fructose metabolism related proteins GLUT5 and KHK and their functions in adenocarcinoma of lung

作　　者：马素珍[1] 刘丹丹[1] 潘晓丽[1] 朱艳琴[1] 

机构地区：[1]河南中医药大学基础医学院实验教学中心,河南郑州450008

出　　处：《暨南大学学报（自然科学与医学版）》2017年第6期509-517,共9页Journal of Jinan University(Natural Science & Medicine Edition)

基　　金：河南省高等学校重点科研项目(16A310021)

摘　　要：目的:检测果糖代谢相关蛋白葡萄糖转运蛋白5(GLUT5)和己酮糖激酶(KHK)在肺腺癌中的表达及生物学功能.方法:利用http://kmplot.com/analysis/上的数据分析GLUT5和KHK的mRNA表达水平对肺腺癌患者生存预后的影响;免疫组织化学方法检测GLUT5和KHK蛋白在肺腺癌及相应癌旁组织中的表达水平;SPSS统计分析GLUT5和KHK表达水平与肺腺癌患者年龄、性别、肿瘤大小、淋巴结转移、远处转移、临床分期、病理分级等临床病理指标之间的关系,以及对患者生存预后的影响;MTT和克隆形成实验检测无葡萄糖条件下果糖对肺腺癌细胞增殖和克隆形成的影响,以及沉默GLUT5和KHK对细胞生物学行为的影响.结果:GLUT5和KHK mRNA表达水平较高的肺腺癌患者,其总生存和无进展生存均较差;GLUT5和KHK在肺腺癌组织中的蛋白表达水平均高于癌旁组织(P<0.01);GLUT5高表达与肿瘤大小、淋巴结转移和病理分化较差有关(P<0.05);KHK高表达与肿瘤大小、临床分期和病理分化较差有关(P<0.05);而且GLUT5和KHK高表达的患者预后较差(P<0.05).果糖可促进肺腺癌细胞的增殖和克隆形成,沉默GLUT5和KHK后,细胞利用果糖的能力显著下降.结论:果糖可以促进肺腺癌细胞的增殖和克隆形成,果糖代谢相关蛋白GLUT5和KHK在肺腺癌组织中高表达,且与肺腺癌的恶性进展密切相关,GLUT5和KHK可作为治疗肺腺癌潜在临床靶点.Aim: To detect the effects of fructose metabolism related proteins GLUT5( glucose transporter,type5) and KHK( ketohexokinase) expressions in adenocarcinoma of lung on prognosis of the patients. Methods: Data from website http://kmplot. Com/analysis/were used to statistically analyze GLUT5 and KHK gene expressions and their effects on prognosis of the patients with adenocarcinoma of lung. Immunohistochemical staining was employed to detect the expression levels of GLUT5 and KHK in adenocarcinoma of lung and matched adjacent non-tumor tissues,and the correlations of GLUT5 andKHK expressions with clinicopathological features( age,sex,differentiation,tumor diameter,Lymphatic metastasis,distant metastasis and clinical stage) were studied using statistical analyses. Kaplan-Meier analysis and Cox proportional hazard modeling were used to assess the overall survival,in order to analyze the effects of GLUT5 and KHK expressions on the prognosis of adenocarcinoma of lung. MTT and twodimensional cloning experiment were used to detect the effects of fructose on tumor cell proliferation,and the effects of sh GLUT5 and sh KHK on use of fructose by the cells. Results: Adenocarcinoma of lung patients with higher expressions of KHK and GLUT5 mRNAs showed poor prognoses. GLUT5 and KHK expressions were significantly higher in adenocarcinoma of lung than the matched adjacent non-tumor tissues( P < 0. 05). GLUT5 expression was significantly correlated with tumor size, Lymphatic metastasis,and pathological differentiation degree( all P < 0. 05). KHK expression was significantly correlated with tumor size,clinical stage,and pathological differentiation degree( all P < 0. 05). In addition,patients with high GLUT5 and KHK levels showed poor survival rates( P < 0. 01).Furthermore,fructose contributes to the growth of adenocarcinoma of lung cell lines,while both shGLUT5 and sh KHK inhibit the use of fructose by the cancer cells. Conclusion: Fructose could promote the proliferation of adenocarcinoma of lung cells. GLUT5 and KHK expressions w

关 键 词：肺腺癌 葡萄糖转运蛋白5(GLUT5) 己酮糖激酶(KHK) 果糖 

分 类 号：R734.2[医药卫生—肿瘤]