Kanyama H, Tomita N, Yamano T, Aihara T, Miyoshi Y, Ohue M, Sekimoto M, Sakita I, Tamaki Y, Kaneda Y, Senter P D, Monden M
Department of Surgery II, Osaka University Medical School, Suita, Japan.
Cancer Res. 2001 Jan 1;61(1):14-8.
To investigate the feasibility of repeated gene transfection in suicide gene therapy against human solid tumors by a combination of 5- fluorocytosine (5-FC) and its converting enzyme, cytosine deaminase (CD), we repeatedly transfected the yeast CD gene into the human pancreatic cancer cell line BXPC3 using the hemagglutinating virus of Japan-liposome in a new gene transfer method. The in vivo growth of the s.c. transplanted BXPC3 tumor in nude mice given CD-gene transfection was significantly suppressed by i.p. injection of 5-FC when compared with tumors treated with the control vector. Furthermore, the tumor transfected with the CD gene during a 7-day interval was suppressed much more than that of a single transfection. These results suggest that repeated transfection of the suicide gene together with the combination of 5-FC and the yeast CD gene using the hemagglutinating virus of Japan-liposome gene transfer method may be useful for the treatment of human solid tumors, including pancreatic cancer.
为了通过5-氟胞嘧啶(5-FC)及其转化酶胞嘧啶脱氨酶(CD)联合应用来研究在自杀基因疗法中对人类实体瘤进行重复基因转染的可行性,我们采用一种新的基因转移方法,即利用日本血凝病毒-脂质体将酵母CD基因反复转染到人胰腺癌细胞系BXPC3中。与用对照载体处理的肿瘤相比,腹腔注射5-FC可显著抑制接受CD基因转染的裸鼠皮下移植BXPC3肿瘤的体内生长。此外,在7天间隔期内用CD基因转染的肿瘤比单次转染的肿瘤受到的抑制作用更强。这些结果表明,使用日本血凝病毒-脂质体基因转移方法将自杀基因与5-FC和酵母CD基因联合进行重复转染,可能对包括胰腺癌在内的人类实体瘤治疗有用。