摘要目的 探讨腺相关病毒介导的趋化因子受体4(CXCR4)短发卡RNA(shRNA)对非小细胞肺癌裸鼠肿瘤生长的抑制作用.方法 采用腺相关病毒介导的CXCR4shRNA抑制人非小细胞肺癌A549细胞中CXCR4的表达,采用实时荧光定量聚合酶链反应(FQ-PCR)检测A549细胞中CXCR4mRNA的表达水平;建立人非小细胞肺癌A549的裸鼠肿瘤模型,分为空病毒组和CXCR4shRNA组,记录两组裸鼠肿瘤体积、质量、数量和生存期,计算裸鼠生存延长率和肿瘤抑制率;取死亡后裸鼠肿瘤组织,采用Westem blot法检测肿瘤组织中血管内皮生长因子(VEGF)的蛋白表达水平.结果 与空病毒组(1.17 ±0.19)比较,重组腺病毒载体感染后的A549细胞CXCR4mRNA表达水平(0.26±0.10)显著下调,差异有统计学意义(P=0.000).CXCR4-shRNA组裸鼠肿瘤平均体积、平均质量和平均数量,显著低于空病毒组,差异有统计学意义(P=0.000).CXCR4-shRNA组平均生存时间显著长于空病毒组(P=0.000);CXCR4-shRNA组的生存延迟率和肿瘤抑制率显著高于空病毒组(P均=0.000),CXCR4-shRNA组VEGF蛋白表达水平(0.28 ±0.05)显著低于空病毒组(1.02±0.23),差异有统计学意义(P=0.000).结论 腺相关病毒介导的CXCR4shRNA能够抑制非小细胞肺癌裸鼠肿瘤的生长及转移.

abstractsObjective To investigate the inhibitory effect of CXC chemokine receptor 4 (CXCR4) short hairpin RNA (shRNA) mediated by recombinant adenovirus vector on tumor growth in nude mice with non small cell lung cancer.Methods Inhibiting the expression of CXCR4 in non-small cell lung cancer cells A549 using CXCR4 shRNA mediated by recombinant adenovirus vector.The expression of CXCR4 mRNA in A549 cells were detected by real-time fluorescent quantitative polymerase chain reaction (FQ-PCR) method.Two groups of nude mice tumor model with non small cell lung cancer were established:the CXCR4 mRNA group and the empty virus group.The tumor volume,quality,quantity and survival time were recorded.The survival rate and tumor inhibition rate of nude mice in two groups were calculated.The expression levels of vascular endothelial growth factor (VEGF) protein in tumor tissue of mice after death was detected by Westem blotting method.Results Compared with the empty virus group (1.17 ±0.19),the expression level of CXCR4 mRNA in A549 cells infected by recombinant adenovirus vector (0.26 ±0.10) significantly decreased (P =0.000).The average volume,mean mass and average number of tumor in group CXCR4-shRNA were significantly lower than that of the nude virus group,(P =0.000).The CXCR4-shRNA group the average survival time was significantly longer than the empty virus group (P =0.000);CXCR4-shRNA group survival rate and delayed tumor growth inhibition rate was significantly higher than that of the empty virus group (P =0.000),CXCR4-shRNA group,VEGF protein expression level (0.28 ±0.05) was significantly lower than that of the empty virus group (1.02 ±0.23),the difference was statistically significant (P =0.000).Conclusion CXCR4 shRNA mediated by recombinant adenovirus vector can inhibit the growth and metastasis in nude mice with non small cell lung cancer.