胞嘧啶脱氨酶／5-氟胞嘧啶自杀基因治疗系统对恶性脑胶质瘤荷瘤裸鼠的抗肿瘤作用

Antitumor efficacy of cytosine deaminase/5-fluorocytosine suicide gene therapy system against malignant gliomas in nude mice

目的评判胞嘧啶脱氨酶／5-氟胞嘧啶（CD／5-FC）自杀基因治疗系统对恶性脑胶质瘤的抗肿瘤效果。方法采用Lipofectamine2000^TM脂质体介导方法将CD基因转染U251恶性胶质瘤细胞系，并接种于裸鼠前臂皮下，成瘤后腹腔注射5-FC（每日500mg/kg体重）10d，观察荷瘤鼠肿瘤的生长情况，8周后比较转染组与对照组肿瘤的体积与重量，并进行病理形态学分析。结果U251细胞获得CD基因的成功转染，5-FC用于不同组别荷瘤裸鼠，8周后转染组肿瘤体积（0．09±0．03）cm^3和重量（0．28±0．11）g明显小于对照组（1．81±0．77）cm^3和（1．63±0．80）g；形态学揭示转染组肿瘤细胞出现明显的凋亡与坏死。结论裸鼠在体实验研究表明：CD／5-FC自杀基因治疗系统是治疗恶性脑胶质瘤行之有效的手段之一。

Objective To explore the antitumor efficacy of cytosine deaminase/5-fluorocytosine （CD/5-FC） suicide gene therapy system against malignant gliomas. Methods CD gene was transferred into U251 malignant glioma cell line using Lipofectamine2000^TM-mediated method. The U251 and U251/ CD cells were seeded into the subcutaneous flank of the nude mice. After tumors appeared,5-FC （500 mg/ kg·day） was subsequently intraperitoneally injected for 10 days. The mice were sacrificed after 8 weeks, the volume and weight of tumors were evaluated. At the same time ,the pathological features were analyzed for the tumor samples. Results The CD gene was successfully transferred into the U251 cells. The in vivo animal data showed that the volume and weight of these implanted tumors were dramatically decreased from （ 1.81 ± 0.77 ） cms to （0.09 ± 0.03） cm^3, and from （ 1.63 ± 0.80） g to （0.28 ± 0.11 ） g,respectively. Morphological observation found cell apoptosis and tumor necrosis in the transfected group. Conclusion These results indicate that the CD/5-FC suicide gene therapy system may serve as one of the main adjuvant strategies in the treatment of malignant gliomas in the future.