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血管内皮生长因子(vascular endothelial growth factor,VEGF)在肿瘤血管生成中起重要作用,并在多数肿瘤中表达上调,为使用针对VEGF的小干扰RNA(VEGF siRNA)治疗肿瘤提供了重要的作用靶点.然而,不清楚VEGF表达的大幅上调是否会影响VEGF siRNA的干扰效率.本文研究VEGF siRNA能否在VEGF的表达大幅上调的鼻咽癌细胞(CNE)中有效抑制VEGF的表达,并进一步研究VEGF siRNA作为潜在的抗癌制剂的应用方法.为增加siRNA的稳定性,对VEGF siRNA进行了2’-脱氧(2’-deoxy)化学修饰,再将修饰后的VEGF siRNA导入经低氧诱导而高表达VEGF的CNE细胞,30h后用ELISA,Western blot结果分析和RT-PCR等方法鉴定其抑制CNE细胞表达VEGF的效果,结果证明VEGF的表达被明显抑制.用化学修饰的VEGF siRNA治疗裸鼠的鼻咽癌移植瘤,将VEGF siRNA与脂质体混合后,注射到肿瘤局部,然后进行超声照射.每周治疗2次,3周以后处死裸鼠、分离肿瘤并测量瘤重.结果显示上述治疗能明显抑制鼻咽癌移植瘤的生长.
Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis and is upregulated in most tumors, providing an important target for the treatment of tumors using VEGF siRNA targeting small interfering RNA However, it is not clear whether a significant upregulation of VEGF expression affects the efficiency of VEGF siRNA interference.In this paper, we investigated whether VEGF siRNA could effectively inhibit the expression of VEGF in nasopharyngeal carcinoma cells (CNE) with a significant upregulation of VEGF expression and further study VEGF siRNA as a potential anticancer agent.In order to increase the stability of siRNA, 2’-deoxy chemical modification of VEGF siRNA was carried out, and then the modified VEGF siRNA was introduced into cells which were induced by hypoxia After 30h, the expression of VEGF in CNE cells was detected by ELISA, Western blot analysis and RT-PCR. The results showed that the expression of VEGF was significantly inhibited. After transplanted nasopharyngeal carcinoma, VEGF siRNA was mixed with liposome and then injected into the tumor site, followed by ultrasound irradiation, twice a week for 3 weeks and then the nude mice were sacrificed to separate the tumor and measure the tumor The results showed that the above treatment can significantly inhibit the growth of nasopharyngeal carcinoma.