P53 ANTISENSE OLIGONUCLEOTIDE INHIBITS GROWTH OF HUMAN COLON-TUMOR AND NORMAL-CELL LINES

We examined the relationship between the expression of mutant p53 prot eins and tumor cell growth using a p53 antisense oligonucleotide (5'-C CCTGCTCCCCCCTGGCTCC-3'). The oligonucleotide inhibited the growth of t hree human colon tumor cell lines (DLD-1, SW620 and WiDr), which produ ce only mutant p53 proteins with different mutation sites. Treatment o f DLD-1 cells with the p53 antisense oligonucleotide caused a decrease in the level of p53 mutant protein. Synthesis of DNA in DLD-1 and SW6 20 cells was inhibited more potently than that of RNA or protein after antisense treatment. Furthermore, these cells were accumulated in the S phase when DNA synthesis was inhibited. Meanwhile, the antisense ol igonucleotide also inhibited the growth of three human normal cell lin es (WI-38, TIG-1 and Intestine 407). While treatment of WI-38 and TIG- 1 cells with the antisense oligonucleotide inhibited synthesis of DNA more potently than that of RNA or protein, these normal cells were acc umulated in the G0/G1 phase. These results suggest that p53 proteins, either with or without mutation, play a pivotal role in the growth of tumor and normal cells, but that mutant and wild-type p53 proteins may function differently in cell growth.