GLUT-1和MMP-2在非小细胞肺癌中的表达及相关性研究

目的:探讨葡萄糖转运蛋白1(GLUT-1)和基质金属蛋白酶-2(MMP-2)在低氧培养条件下肺腺癌细胞株A549及非小细胞肺癌(NSCLC)组织中的表达及临床意义。方法:分别采用免疫印迹(Western Blot)、免疫组化法测定缺氧条件下A549细胞及80例NSCLC组织和26例癌旁正常肺组织中GLUT-1和MMP-2的蛋白表达,并分析GLUT-1、MMP-2与临床病理特点之间的关系及两者相互关系。结果:随着缺氧时间的延长,肺腺癌细胞中GLUT-1和MMP-2的蛋白水平呈升高趋势(P<0.01或P<0.05)。NSCLC组织中GLUT-1和MMP-2的蛋白阳性表达率明显高于癌旁正常肺组织(P<0.01)。有淋巴结转移的表达高于无淋巴结转移者,中晚期(Ⅲ+Ⅳ期)肺癌组织中的表达高于早期(Ⅰ+Ⅱ期)(P<0.05或P<0.01)。GLUT-1与MMP-2表达呈正相关(P<0.01)。结论:氯化钴诱导缺氧可以上调GLUT-1和MMP-2在肺腺癌细胞中的表达,使之进一步耐受缺氧。HIF-1α、GLUT-1在NSCLC组织中过度表达,两者协同参与了非小细胞肺癌的侵袭转移。

Study of expression and correlation of GLUT-1 and MMP-2 in non-small cell lung cancer

Objective:To investigate the expression and clinical significance of glucose transporter-1(GLUT-1) and matrix metalloproteinase-2(MMP-2) in hypoxic human lung adenocarcinoma cell line A549 and humun non-small cell lung cancer(NSCLC) tissues. Methods: Western Blot was used to determine the changes of GLUT-1 and MMP-2 in hypoxic lung adenocarcinoma cells. The expression of GLUT-1 and MMP-2 was detected the immunohistochemidal method in 80 specimens of NSCLC and 26 specimens of adjacent non-cancerous lung tissues.Their interrelations and relationship with the pathological characteristics of the tumors were analyzed. Results: After hypoxia exposure, the protein expression increased time-dependentedly. (P<0.01 or P<0.05). In NSCLC,the positive expression rates of GLUT-1 proteins were higher than that in normal tissues(P< 0.01). Comparing with the protein levels of GLUT-1 and MMP-2 in NSCLC of ⅠandⅡstage, there was markedly increased in Ⅲand Ⅳstage (P<0.01) .The expression of GLUT-1 and MMP-2 in group of lymph node metastasis was higher than that in group without lymph node metastasis (P<0.05). GLUT-1 protein levels showed positive correlations with MMP-2 levels(r=0.436,P<0.01).Conclusion: CoCl2 can up-regulate the expression of GLUT-1 and MMP-2 in lung adenocarcinoma cell line A549 by inducing hypoxia. The overexpression of GLUT-1 and MMP-2 might play synergetic roles in invasion and metastasis of NSCLC.