SIAH2与MMP2在非小细胞肺癌中的表达及其意义

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摘要目的：研究SIAH2与金属基质蛋白酶2（MMP2）在人非小细胞肺癌（NSCLC）中的表达，并分析其与肺癌临床病理特征的关系。方法：采用免疫组织化学S-P法检测120例NSCLC石蜡包埋组织中SIAH2与MMP2蛋白的表达情况，分析其表达与临床病理因素之间的相关性。采用脂质体介导法将SIAH2干扰片段SIAH2 siRNA转染入肺癌细胞系A549和SK-MES-1后，利用RT-PCR和Western blot法检测SIAH2与MMP2在mRNA和蛋白水平的表达情况。干扰SIAH2表达后，应用MTT法、Transwell法检测SIAH2对肺癌细胞增殖和侵袭的影响。结果：SIAH2与MMP2在NSCLC中高表达，其高表达与肺癌高TNM分期（P=0.019，P=0.020）、低分化（P=0.024，P=0.011）和淋巴结转移（P=0.032，P=0.021）显著相关。SIAH2与MMP2在NSCLC中表达呈正相关（r=0.321，P＜0.01），SIAH2与MMP2在肺癌细胞系中高表达。干扰SIAH2表达后，与未处理组及转染对照片段control siRNA组相比，SIAH2与MMP2的mRNA（P＜0.05）和蛋白（P＜0.05）表达均明显下降，细胞生长增殖能力[P＜0.01（2～4 d）；P＜0.01（2～4 d）]减弱，细胞侵袭数目（17.61±4.34；20.12±5.43）（P＜0.05）减少。结论：高表达SIAH2在NSCLC的恶性进程中起重要作用，MMP2可能参与了此恶性表型的形成过程。

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关键词 ：癌, 非小细胞肺；SIAH2；金属基质蛋白酶2；增殖；侵袭

Abstract：Objective: To study the SIAH2 and MMP2 expression in non-small cell lung cancer (NSCLC), and analyze the relationship between the expression and clinical pathological features and the malignant degree of lung cancer. Methods: Immunohistochemistry S-P method was used to examine the expression of SIAH2 and MMP2 protein in 120 paraffin-embeded specimens with NSCLC, and analyzed the correlation between the expression and clinical pathological factors. The expressions of SIAH2 and MMP2 were detected by RT-PCR and Western blot in lung cancer cell lines. We transfected SIAH2 siRNA into A549 and SK-MES-1 cells using Lipofectamine 2000, and then detected the SIAH2 and MMP2 mRNA and protein expression by RT-PCR and Western blot, thus tested the cell proliferation and cell invasion by MTT and Transwell respectively. Results: Immunohistochemical analysis showed that SIAH2 and MMP2 expression levels were significantly higher in NSCLC tissues and significantly associated with the higher TNM stage (P=0.019, P=0.020), poor differentiation (P=0.024, P=0.011), and lymph node metastasis (P=0.032, P=0.021). SIAH2 protein expression was positively correlated with MMP2 in NSCLC (r=0.321, P<0.01). The expression of SIAH2 and MMP2 were higher in lung cancer cells than in normal bronchial epithelial cell (P<0.05). Compared with the untreated and control siRNA group, the levels of SIAH2 and MMP2 mRNA and protein were decreased in the cells transfected with the SIAH2 siRNA, respectively (P<0.05). The proliferation rate [P<0.01 (day 2-4); P<0.01 (day 2-4)] was slower, and invasion number (17.61±4.34; 20.12±5.43) was decreased in the cells transfected with the SIAH2 siRNA (P<0.05). Conclusion: Up-regulation of SIAH2 plays an important role in the process of malignant phenotype in human NSCLC, and MMP2 may be involved in this process.

Key words： carcinoma, non-small cell lung seven in absentia homolog matrix metalloproteinase prolifer-ation invasion

收稿日期: 2016-06-22

基金资助:国家自然科学基金资助项目（81201853）；浙江省自然科学基金资助项目（LY16H160058）；浙江省医药卫生科技计划资助项目（2015121805）。

通讯作者: 温媛媛，副主任医师，Email：wenyuanyuan@sina.cn。

作者简介: 杨志强（1981-），男，山西临汾人，主治医师，博士。

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2017/V47/I3/168

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