瘤内siRNA干扰血管内皮生长因子对恶性黑色素瘤的放射增敏作用

Effect of siRNA interfering vascular endothelial growth factor on radiation sensitization of malignant melanoma

目的研究瘤内siRNA干扰VEGF的表达对恶性黑色素瘤放射敏感性的影响。方法首先建立恶性黑色素瘤A375细胞的裸鼠移植瘤模型,采用脂质体包裹的小RNA干扰技术,将恶性黑色素瘤移植瘤裸鼠随机分为空白对照组、VEGF阴性质粒组、VEGF阳性质粒组,每周2次测肿瘤体积,计算肿瘤体积抑瘤率;HE染色进行组织形态学观察,计算肿瘤横断面坏死面积率;免疫组化法测定瘤体血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达。结果 VEGF阳性质粒组VEGF的表达减弱(P<0.05),VEGF阳性质粒组有较多的组织坏死,肿瘤生长明显抑制(P<0.05)。结论瘤内注射脂质体包裹的siRNA-VEGF对恶性黑色素瘤有放射增敏作用,为临床开展针对VEGF基因的靶向治疗和放射治疗的联合治疗恶性黑色素瘤提供了实验依据。

Objective To investigate the role of a small RNA interference against VEGF in radiation sensitivity in melanoma .Methods A375 human melanoma cell lines were transplanted into nude mice ,which with malignant melanoma were randomly divided into control group , VEGF negative plasmid group and VEGF positive plasmid group, followed by 4Gy irradiation twice a week for 2 weeks.The volume of tumor was calculated twice a week, the area of tumor necrosis was assayed by HE,the expression of VEGF in tumor was determined by Western-blot and Immunohistochemical. ResuIts The expression of VEGF in VEGF positive plasmid group decreased significantly (P<0.05), VEGF positive group had more tissue necrosis, tumor growth was significantly inhibited (P<0.05).ConcIusion siRNA-VEGF in tumor injection liposome encapsulated in malignant melanoma has a role in the radiation sensitization, which provides an experimental basis for the clinical development of targeted therapy combined with radiotherapy for the treatment of VEGF gene.