Perlaky L, Saijo Y, Busch R K, Bennett C F, Mirabelli C K, Crooke S T, Busch H
Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030.
Anticancer Drug Des. 1993 Feb;8(1):3-14.
The human nucleolar antigen p120 was detected with an anti-p120 monoclonal antibody (MAbp120) in most human malignant tumors (Freeman et al., Cancer Research, 48, 1244-1251, 1988). Stable transfection of the sense p120 cDNA caused malignant transformation of NIH/3T3 cells in vitro, and the antisense p120 constructs markedly delayed the growth of these transformed cells (Perlaky et al., Cancer Research, 52, 428-436, 1992). Several p120 antisense phosphorothioate oligonucleotides designed to hybridize with different regions of the p120 sequence were screened on human tumor cell lines in vitro. Marked growth inhibition of HeLa, LOX and HRCC cell lines was found, particularly with antisense p120 oligonucleotide ISIS 3466 in combination with N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA); oligonucleotide ISIS 3466 is complementary to a non-translated region at the 3' end of the molecule. Preliminary in vivo studies on human LOX ascites tumor in nude mice showed marked inhibitory effects on tumor growth by the antisense oligonucleotide ISIS 3466 in the presence of DOTMA when treated on alternate days.
用人抗p120单克隆抗体（MAbp120）在大多数人类恶性肿瘤中检测到人类核仁抗原p120（弗里曼等人，《癌症研究》，第48卷，第1244 - 1251页，1988年）。正义p120 cDNA的稳定转染导致NIH/3T3细胞在体外发生恶性转化，而反义p120构建体显著延迟了这些转化细胞的生长（佩拉基等人，《癌症研究》，第52卷，第428 - 436页，1992年）。在体外对几种设计用于与p120序列不同区域杂交的p120反义硫代磷酸酯寡核苷酸在人肿瘤细胞系上进行了筛选。发现对HeLa、LOX和HRCC细胞系有明显的生长抑制作用，特别是反义p120寡核苷酸ISIS 3466与N - [1 - （2,3 - 二油酰氧基）丙基] - N，N，N - 三甲基氯化铵（DOTMA）联合使用时；寡核苷酸ISIS 3466与该分子3'端的一个非翻译区域互补。对裸鼠体内人LOX腹水瘤的初步研究表明，当隔天给药时，在DOTMA存在的情况下，反义寡核苷酸ISIS 3466对肿瘤生长有明显的抑制作用。
