pAdKDR-tk自杀基因系统靶向杀伤鼻咽癌肿瘤血管的体内研究

目的探讨pAdKDR-tk自杀基因系统靶向杀伤肿瘤血管对鼻咽癌的治疗作用。方法将24只鼻咽癌荷瘤裸鼠随机分成3组,分别于0、1、7d向瘤体内注入重组腺病毒液0.1mL。第2次注射病毒液时,组Ⅰ、组Ⅱ、组Ⅲ分别腹腔注射pAdKDR-tk/PBS、pAdKDR-tk/GCV和pAdCMV-tk/GCV100mg/kg,每天1次,连续10d。观察治疗前后肿瘤体积、病理及微血管密度变化。结果组Ⅲ裸鼠移植肿瘤缩小速度最快,组Ⅱ次之,而组Ⅰ增大。病理检查显示组Ⅱ、Ⅲ肿瘤出现不同程度坏死,坏死灶中心位于病毒液注射部位。Ⅷ因子相关抗原免疫组化检查发现肿瘤血管密度组Ⅱ最低,组Ⅰ最高,两组之间差异具有统计学意义(P<0.01)。结论 pAdKDR-tk自杀基因系统对鼻咽癌肿瘤血管有良好的靶向杀伤效应,从而达到破坏肿瘤细胞的作用。

In vivo study on pAdKDR-tk suicide gene system targeting tumor vessels of nasopharyngeal carcinoma

Objective To explore the therapeutic effect of pAdKDR-tk suicide gene system on tumor vascular injury of nasopharyngeal carcinoma （NPC）. Methods Twenty-four nude mice with NPC inoculation were randomly dividied into 3 groups, and received intratumoral injection of 0.1 mL recombinant adenovirus solution on days 0, 1 and 7. At the second injection of recombinant adenovirus, Groups Ⅰ, Ⅱ and Ⅲ were intraperitoneally injected with 100 mg/kg of pAdKDR-tk/PBS, pAdKDR-tk/GCV and pAdCMV-tk/GCV once daily for 10 days, respectively. Tumor size, pathology and microvessel density were observed before and after treatment. Results The implanted tumor shrank obviously in Group Ⅱ and moderately in Group Ⅲ, but enlarged in Group Ⅰ. Pathological examination depicted the tumor necrosis in Groups Ⅱ and Ⅲ, with the necrotic centre locating in the injection site. Factor Ⅷ related antigen immunostaining revealed that tumor microvessel density was lower in Group Ⅱ than that in Group I （P0.01）. Conclusion pAdKDR-tk suicide gene system has a good targeted killing role in the tumor vessels of NPC, resulting in the destruction of neoplasm cells.