HSV-tk基因和IL-12基因抑制VEGF的表达及对鼻咽癌荷瘤裸鼠模型放射增敏作用的实验研究  

Experimental Study of HSV-tk Gene and IL-12 Gene Inhibiting VEGF Expression and Radiosensitization Effect on Nasopharyngeal Carcinoma Tumor Bearing Nude Mouse Models

作　　者：周玉华 朱欠元 曾友根 李宝金 ZHOU Yuhua;ZHU Qianyuan;ZENG Yougen;LI Baojin(Ji’an Third People's Hospital,Jiangxi Province,Ji’an 343000,China)

机构地区：[1]江西省吉安市第三人民医院,江西吉安343000 [2]井冈山大学临床医学院 [3]广州医科大学附属市八医院

出　　处：《中国医学创新》2023年第19期24-27,共4页Medical Innovation of China

基　　金：国家自然科学基金资助项目(81350022);江西省教育厅科技计划项目(GJJ201025)。

摘　　要：目的:研究HSV-tk基因和IL-12基因抑制血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达对鼻咽癌荷瘤裸鼠模型放射增敏作用。方法:建立鼻咽癌荷瘤裸鼠模型,将42只成瘤鼠随机分成IL-12组、IL-12+放射治疗组、HSV-tk/GCV组、HSV-tk/GCV+放射治疗组、IL-12+HSV-tk/GCV组、IL-12+HSV-tk/GCV+放射治疗组、空白对照组、每组6只。采用瘤内注射分别给予相对应的重组腺病毒液(AdKDR-tk)、重组逆转录腺病毒液IL-12及生理盐水,24 h后重复注射1次。次日起HSV-tk/GCV组、HSV-tk/GCV+放射治疗组、IL-12+HSV-tk/GCV组、IL-12+HSV-tk/GCV+放射治疗组连续10 d每天腹腔内注射GCV 100 mg/(kg·d),连续10 d。各放射治疗组第3周开始给予6MV-X照射,每天2 Gy,连续5 d。治疗结束后处死裸鼠,检测裸鼠肿瘤质量及肿瘤生长抑制率,免疫组织化学法检测肿瘤微血管密度及VEGF阳性细胞灰度值。结果:IL-12+HSV-tk/GCV+放射治疗组裸鼠瘤体质量明显低于IL-12组、IL-12+放射治疗组、HSV-tk/GCV组、HSV-tk/GCV+放射治疗组,差异均有统计学意义(P<0.05)。IL-12+HSV-tk/GCV+放射治疗组的肿瘤生长抑制率最高,达71.7%。IL-12+HSV-tk/GCV+放射治疗组微血管密度均低于其他各组,VEGF阳性细胞灰度值均高于其他各组(P<0.05)。结论:HSV-tk基因和IL-12基因联合应用在鼻咽癌荷瘤裸鼠模型放疗中可抑制移植瘤的生长,为鼻咽癌的放疗产生增敏作用。Objective:To investigate the radiosensitization effect of HSV-tk gene and IL-12 gene on the expression of vascular endothelial growth factor(VEGF)in nasopharyngeal carcinoma tumor bearing nude mouse models.Method:A nude mouse model of nasopharyngeal carcinoma was established,and 42 tumor-forming mice were randomly divided into IL-12 group,IL-12+radiotherapy group,HSV-tk/GCV group,HSV-tk/GCV+radiotherapy group,IL-12+HSV-tk/GCV+radiotherapy group,blank control group,and 6 mice in each group.The corresponding recombinant adenopathy venom(AdKDR-tk),recombinant retrograde adenopathy venom IL-12 and normal saline were given by intratumoral injection,and the injection was repeated once 24 hours later.From the next day,the HSV-tk/GCV group,the HSV-tk/GCV+radiotherapy group,the IL-12+HSV-tk/GCV group,and the IL-12+HSV-tk/GCV+radiotherapy group were intraderally injected 100 mg/(kg·d)of GCV every day for 10 consecutive days.Each radiotherapy group was given 6MV-X irradiation at 2 Gy per day for 5 consecutive days starting from the 3rd week.After treatment,the nude mice were killed,the tumor quality and tumor growth inhibition rate were detected,and the tumor microvascular density and positive expression of gray value of VEGF positive cells were detected by immunohistochemical methods.Result:The tumor mass of nude mice in IL-12+HSV-tk/GCV+radiotherapy group was significantly lower than those in IL-12 group,IL-12+radiotherapy group,HSV-tk/GCV group and HSV-tk/GCV+radiotherapy group,with statistical significance(P<0.05).The tumor growth inhibition rate of IL-12+HSV-tk/GCV+radiotherapy group was the highest,reaching 71.7%.The microvascular density and gray value of VEGF positive cells in IL-12+HSV-tk/GCV+radiotherapy group were lower than those in other groups(P<0.05).Conclusion:The combined application of HSV-tk gene and IL-12 gene can inhibit the growth of transplanted tumor in the nude mouse model of nasopharyngeal carcinoma,and produce sensitization for the radiotherapy of nasopharyngeal carcinoma.

关 键 词：血管内皮生长因子 鼻咽癌 放射治疗 HSV-TK 基因 IL-12 基因 

分 类 号：R739.63[医药卫生—肿瘤]