羟甲基无环鸟苷对携有单纯疱疹病毒胸腺嘧啶核苷激酶基因人卵巢癌裸鼠皮下移植瘤生长的抑制作用  

Inhibitory Effect of Ganciclovir on the HSV1tk Positive Subcutaneous Tumors Transplanted with Human Ovarian Cancer in Nude Mice

作　　者：徐丛剑[1,2,3] 张惜阴[1,2,3] 金志军[1,2,3] 姚明 周先荣[1,2,3] 丰有吉[1,2,3] 许秀兰 顾健人[1,2,3] 

机构地区：[1]上海医科大学妇产科医院 [2]第二军医大学长征医院妇产科 [3]上海市肿瘤研究所

出　　处：《中华妇产科杂志》1997年第12期709-711,I044,共4页Chinese Journal of Obstetrics and Gynecology

基　　金：国家自然科学基金

摘　　要：目的：观察羟甲基无环鸟苷（ＧＣＶ）对携有Ⅰ型单纯疱疹病毒胸腺嘧啶核苷激酶基因（ＨＳＶ１－ｔｋ）的人卵巢上皮癌ＡＯ细胞的体内杀伤效应。方法：于裸鼠背部左右两侧皮下分别接种ＡＯ细胞及携有ＨＳＶ１－ｔｋ基因的ＡＯ细胞（ＡＯ／ＨＳＶ１－ｔｋｃ），成瘤后每日腹腔注射ＧＣＶ。结果：经ＧＶＣ治疗后，裸鼠背部两侧肿瘤平均重量分别为：左侧ＡＯ肿瘤０．６８１ｇ；右侧ＡＯ／ＨＳＶ１－ｔｋｃ肿瘤０．０８７ｇ。经ＧＣＶ作用后仍然存活的多数ＡＯ／ＨＳＶ１－ｔｋｃ细胞胞浆呈肥大、坏死表现。但其核内染色质却多呈异染色质状态。结论：ＧＣＶ在裸鼠体内代谢后仍可高效杀伤携有ＨＳＶ１－ｔｋ基因的卵巢癌细胞，从而抑制肿瘤生长。但仍然存活的肿瘤细胞增殖活跃，如加用Ｓ期特异的化疗药物可能进一步提高远期疗效。Objective: To investigate the inhibitory effect in vivo of ganciclovir (GCV) on the growth of human ovarian cancer cells (AO) transducted with the thymidine kinase gene of herpes simplex virus Ⅰ type (HSV1tk). Methods: Tumors were induced in nude mice by subcutaneous injection of AO cells and AO cells carried with HSV1tk gene from China strain (AO/HSV1tkc cells). When the growing tumors were visible, GCV was injected daily into the peritoneum of the nude mice. Results: The average weights of survived AO/HSV1tkc tumors and AO tumors treated with GCV were 0.087±0.036 g and 0.661±0.260 g respectively. Most of the survived AO/HSV1tkc cells treated with GCV were characterized by hypertrophy and necrosis, but their nuclear chromatins predominantely took the forms of heterchromatins. Conclusions: GCV could effectively inhibit the growth of HSV1tk positive human ovarian cancer cells in vivo, but the nuclei of the survival tumor cells appeared to proliferate actively. As the same results of in vitro experiments, this may suggest that HSV1tk/GCV gene therapeutic system might be combined with Sphase chemotherapy to increase the longterm effect.

关 键 词：卵巢肿瘤 基因治疗 羟甲基无环鸟苷 HSV1-TK 

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