血红素加氧酶-1在人肺癌细胞中的表达及其对血管生成因子的影响

Expression of heme oxygenase-1 and its effect on VEGF in human lung cancer cells

目的探讨血红素加氧酶-1(HO-1)在人肺癌细胞中的表达及其对肺癌血管内皮生长因子(VEGF)的影响和可能的作用机制。方法选用肺腺癌细胞株A549和肺鳞癌细胞株SK-MES-1为研究对象,以永生化支气管上皮细胞株HBE为对照,采用qRT-PCR法同时检测三个细胞株中HO-1和VEGF基因的表达;采用Western Blotting法检测三个细胞株中HO-1蛋白的表达;用四甲基偶氮唑(MTT)法检测细胞增殖。结果与HBE比较,A549和SK-MES-1中的HO-1不管在mRNA水平(P<0.05)还是在蛋白水平上都明显表达增高,A549较SK-MES-1中HO-1mRNA表达增高(P<0.05);qRT-PCR结果显示,VEGF在两个肺癌细胞株中的表达均显著增高(P<0.05),两个肺癌细胞株中HO-1和VEGF的表达增高具有相关性(相关系数分别为1.35和9.80)。结论 HO-1在肺癌细胞中表达增高,且对VEGF生成产生影响,由此推测,HO-1通过促进VEGF表达促进血管生成,从而影响肺癌生长及转移,这可能是HO-1作用于肺癌的机制之一。

Objective To investigate expression of heme oxygenase-1（HO-1）,its effect on vascular endothelial growth factor（VEGF） and probable mechanism in human lung cancer cells.Methods Taking the lung adenocarcinoma cell line A549 and squamous cell line SK-MES-1 as research objects and the immortalized bronchial epithelial cell line HBE as the control,expressions of HO-1mRNA and VEGF mRNA in lung cancer cell lines and normal lung cell line were detected by Real-time quantitative PCR.Then,protein expression of HO-1 was detected by Western Blot.MTT assay was used to detect cell proliferation.Results Both HO-1 mRNA and protein expressions were obviously increased in human lung cancer cell lines compared with HBE（P0.05）,and HO-1mRNA had a higher level in A549 than in SK-MES-1（P0.05）.VEGF mRNA expression was also increased in human lung cancer cell lines compared with HBE（P0.05）,and increases in expressions of HO-1and VEGF were correlated in the two lung cancer cell lines（correlation coefficients were 1.35 and 9.80,respectively）.Conclusion HO-1 expression increases and plays an important role in VEGF synthesis.Its probable mechanism is that HO-1 promotes angiogenesis by enhancing expression of VEGF,thereby affecting the growth and metastasis of lung cancer.