腺病毒介导胸苷激酶基因治疗卵巢癌的动物试验研究  

Animal Experiment on Gene Therapy of Ovarian Cancer by AdenovirusMediated Thymidine Kinase Gene Transduction and Ganciclovir Administration in Vivo

作　　者：童晓文[1,2,3] 施维 顾美皎 D.G.Kieback[1,2,3] 

机构地区：[1]同济医科大学协和医院妇产科 [2]同济医院 [3]美国Baylor医学院

出　　处：《中华妇产科杂志》1997年第12期712-714,I045,共4页Chinese Journal of Obstetrics and Gynecology

摘　　要：目的：探讨腺病毒介导Ｒｏｕｓ肉瘤病毒驱动的单纯疱疹病毒胸苷激酶（ＡＤＶ／ＲＳＶ－ｔｋ）基因及丙氧鸟苷（ＧＣＶ）治疗卵巢癌的有效性和毒性。方法：首先以卵巢浆液性腺癌细胞系Ｏｖ－ｃａ－２７７４建立荷人卵巢癌裸鼠腹水瘤模型，再分别单用ＡＤＶ／ＲＳＫ－ｔｋ或ＧＣＶ（单药组）或联合应用ＡＤＶ／ＲＳＫ－ｔｋ及ＧＣＶ（联合用药组）进行治疗。观察空白对照组、单药组及联合用药组裸鼠的平均生存时间及药物毒性。结果：单药组裸鼠在用药后１４．４±１．７天～１９．３±３．５天死亡，与空白对照组相比，差异无显著性。而联合用药组裸鼠的平均生存时间比单药组至少延长两倍，两组差异有显著性；开始用药时间越早，平均生存期越长；且疗效与用药剂量及裸鼠肿瘤负荷有依赖关系。结论：对荷人卵巢癌裸鼠腹水瘤模型的ＡＤＶ／ＲＳＴ－ｔｋ基因治疗是一种安全、有效的方法。Objective: The efficacy and toxicity of adenovirusmediated transduction of herpes simplex virus thymidine kinase gene started by Rous sarcoma virus (ADV/RSVtk) followed by administration of ganciclovir (GCV) were studied in vivo. Methods: An animal model of human epithelial ovarian cancer was established in nude mice using the serous ovarian adenocarcinoma cell lines Ovca2774, then mice were treated by ADV/RSVTk and GCV, or GCV and HSVtk respectively. The average survival time of mice and toxicity were assessed.Results: The mice treated with GCV or HSV tk alone died from 14.4±1.7 to 19.3±3.5 days after treatment. The survival time had no difference with control group. The mice treated with ADV/RSVtk followed by GCV lived at least two times longer than controls and the difference in both groups was significant. The earlier the treatment began, the longer the average survival time was. Treatment efficacy was dependent on dose of ADV/RSVtk and tumor burden of mice. Conclusion: ADV/RSVtk gene therapy is a safe and efficient approach to ovarian cancer treatment in the experiment. 

关 键 词：卵巢肿瘤 胸苷激酶 基因治疗 腺病毒 

分 类 号：R737.310.5[医药卫生—肿瘤] R394[医药卫生—临床医学]