胞嘧啶脱氨酶基因与前体药物5-氟胞嘧啶联合应用对人乳腺癌裸鼠模型的实验治疗

Experimental therapy for the human breast carcinoma with cytosine deaminase gene and prodrug 5 fluorocytosine in nude mice

探讨胞嘧啶脱氨酶（ＣＤ）基因与前体药物５－氟胞嘧啶（５－ＦＣ）对人乳腺癌裸鼠移植瘤的抗肿瘤作用．应用细胞克隆形成实验及裸鼠移植瘤模型研究ＣＤ／５－ＦＣ体系的抗肿瘤作用．５－ＦＣ０．５和１．０ｇ·Ｌ－１对转基因人乳腺癌细胞的克隆形成抑制率分别为９０％和９５％，显著高于未转基因的人乳腺癌细胞；５－ＦＣ（０．５ｇ·ｋｇ－１·ｄ－１ｉｐ，１４ｄ）治疗组的转基因人乳腺癌裸鼠移植瘤的瘤重和生长速度均显著低于未转基因的移植瘤．结果表明ＣＤ／５－ＦＣ体系对人乳腺癌裸鼠移植瘤有显著的的抗肿瘤作用．

As to investigate the antitumor activity of cytosine deaminase(CD)gene and prodrug 5 fluorocytosine(5 FC)for human breast carcinoma in nude mice, the clonogenic assay and xenografts model in nude mice were used. It was found that the inhibition rate of clonogenic forming unit of transgenic human breast carcinoma cells treated with 5 FC at concentrations of 0.5 and 1.0 g·L 1 was significantly greater than that of non transgenic human breast carcinoma cells (90% and 95% vs 6% and 51%). Administration of 5 FC 0.5 g·kg 1 ip, once a day for 14 d, the tumor weight and tumor growth rate of xenografts tumors of transgenic breast carcinoma were significantly lower than that of non transgenic xenograft tumors in nude mice. The experiments suggest that CD/5 FC system possesses significant antitumor activity on human breast carcinoma in nude mice.