GROWTH-INHIBITION OF HUMAN TUMOR-CELL LINES BY ANTISENSE OLIGONUCLEOTIDES DESIGNED TO INHIBIT P120 EXPRESSION

The human nucleolar antigen p120 was detected with an anti-p120 monocl onal antibody (MAbp120) in most human malignant tumors (Freeman et al. , Cancer Research, 48, 1244-1251, 1988). Stable transfection of the se nse p120 cDNA caused malignant transformation of NIH/3T3 cells in vitr o, and the antisense p120 constructs markedly delayed the growth of th ese transformed cells (Perlaky et al., Cancer Research, 52, 428-436, 1 992). Several p120 antisense phosphorothioate oligonucleotides designe d to hybridize with different regions of the p120 sequence were screen ed on human tumor cell lines in vitro. Marked growth inhibition of HeL a, LOX and HRCC cell lines was found, particularly with antisense p120 oligonucleotide ISIS 3466 in combination with [1-(2,3-dioleyloxy)prop yl]-N,N,N-trimethylammonium chloride (DOTMA); oligonucleotide ISIS 346 6 is complementary to a non-translated region at the 3' end of the mol ecule. 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 al ternate days.