胞嘧啶脱氨酶基因联合5-氟胞嘧啶对卵巢癌裸鼠移植瘤的抑制作用

Anticancer effects of cytosine deaminase gene/5-fluorocytosine therapies to ovarian cancer in vivo

目的 了解胞嘧啶脱氨酶 (CD)基因联合 5 氟胞嘧啶 (5 FC)对卵巢癌裸鼠皮下移植瘤生长的抑制作用。方法 应用胚肾 2 93细胞扩增整合有CD基因的复制缺陷的腺病毒 ,并将其分离、提纯。以卵巢癌裸鼠模型作为研究对象。实验组 (5只 ) :将整合有CD基因的复制缺陷的腺病毒 0 1ml[1×10 10 菌斑形成单位 (pfu) /ml]注入瘤体内 ,隔日 1次 ,共 3次 ;同时将 5 FC按每次 4 0 0mg/kg注入裸鼠腹腔内 ,每日 2次 ,共 7d。对照组 (5只 ) :以同样方法将同体积生理盐水注入裸鼠体内。观察两组裸鼠的肿瘤生长速度及倍增时间。结果 (1)整合有CD基因的腺病毒滴度为 1 0 7× 10 10 pfu/ml。 (2 )实验组裸鼠肿瘤生长明显受抑制 ,肿瘤体积由 9mm3 增加到 85 5mm3 ,而对照组肿瘤体积由 7mm3 增加到 2 0 14mm3 ,两组比较 ,差异有显著性 (P <0 0 5 ) ,这种显著性差异在用药结束后约 2 0d才表现出来 ,并维持约 30d。(3)实验组与对照组肿瘤倍增时间分别为 (8 1± 0 7)d和 (6 4± 0 7)d ,两组比较 ,差异有显著性 (P<0 0 5 )。结论 应用CD基因联合 5

Objective To evaluate the anticancer effects of cytosine deaminase (CD) gene/5 fluorocytosine (5 FC) to human ovarian papillary serous cystadenocarcinoma in nude mice Methods Replication deficient adenovirus containing CD gene was used to transfect human embryonal kidney cell line 293, and the adenovirus′s concentration was up to 1×10 10 pfu (plaque forming unit)/ml after purification Ten female BULB/C nude mice were implanted subcutaneously with approximate 0 08 g tissue of ovarian papillary serous cystadenocarcinoma from the parental generation, and they were divided into test group and control group While the tumors grew with diameter of approximate 3mm, test group received intratumoral injections of adenovirus CD at 1×10 9 pfu in a 100 μl volume on day 1, 3, 5 These animals were administered 5 FC at doses of 400 mg/kg twice daily by intraperitoneal injection from day 1 to day 7 Normal saline was used in control group with the same volume and by the same methods Tumor volumes were measured in following days Results (1) Compared with control group, the growth of tumors in test group was significantly suppressed Twenty days after the therapies, the tumor volumes in test group and control group were (91±68) mm 3 and (238± 122) mm 3 respectively, there was significant difference This difference lasted for approximately 30 days ( P =0 045-0 019) (2) The mean time of tumor volume doubling in test group and control group were (8 1±0 7)days and (6 4±0 7) days, respectively ( P <0 05) Conclusions This research has shown the significant effects of CD gene/5 FC on human ovarian cancer in nude mice model The results may be the important basis of clinical trials They suggest that this toxic gene/prodrug therapy system may play an important role in ovarian cancer therapy in the future