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目的:探讨硫修饰和脂质体包裹的反义寡核苷酸(ASODN)抑制Lewis肺癌细胞血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)基因表达的效应,减少肺切除导致的呼吸功能衰竭发生的可能性。方法:将经脂质体包裹并部分硫代修饰后的VEGFASODN,正义寡核苷酸(SODN),错义寡核苷酸(MODN)加入培养的Lewis肺癌细胞中,采用免疫组织化学SP法及RT-PCR技术检测肺癌细胞中VEGF蛋白及VEGFmRNA表达,同时测定各上清液刺激血管内皮细胞生长的受抑情况。结果:VEGFASODN能明显抑制Lewis肺癌细胞VEGF蛋白及VEGFm-RNA的表达,而且可以通过抑制VEGF的表达抑制内皮细胞的生长,并对内皮细胞的抑制作用存在浓度依赖性,5,10,20μmol/L浓度组的内皮细胞生长抑制率分别约为13.77%,48.85%,76.29%。VEGFSODN和VEGFMODN却无此作用。结论:VEGFASODN抑制肺癌细胞表达VEGF,进而抑制内皮细胞生长,可以成为肺癌基因治疗的一种新的策略。
Objective: To investigate the effect of sulfur modification and ASODN on the gene expression of vascular endothelial growth factor (VEGF) in Lewis lung carcinoma cells and to reduce the possibility of respiratory failure caused by lung resection . Methods: VEGFASODN, sense oligonucleotide (SODN) and missense oligonucleotide (MODN), which were encapsulated by liposomes and partially thio-modified, were added to cultured Lewis lung cancer cells. Immunohistochemical SP method and The expression of VEGF protein and VEGF mRNA in lung cancer cells were detected by RT-PCR, and the inhibitory effect of each supernatant on the growth of vascular endothelial cells was also determined. Results: VEGFASODN could significantly inhibit the expression of VEGF protein and VEGFm-RNA in Lewis lung cancer cells, and could inhibit the growth of endothelial cells by inhibiting the expression of VEGF. The inhibitory effect of VEGFASODN on endothelial cells in a concentration-dependent manner, 5,10,20μmol / L Concentration group of endothelial cell growth inhibition rates were about 13.77%, 48.85%, 76.29%. VEGFSODN and VEGFMODN have no such effect. Conclusion: VEGFASODN inhibits the expression of VEGF in lung cancer cells and then inhibits the growth of endothelial cells, which may be a new strategy for gene therapy of lung cancer.