p53 antisense oligonucleotide inhibits growth of human colon tumor and normal cell lines.
We examined the relationship between the expression of mutant p53 proteins and tumor cell growth using a p53 antisense oligonucleotide (5'-CCCTGCTCCCCCCTGGCTCC-3'). The oligonucleotide inhibited the growth of three human colon tumor cell lines (DLD-a, SW620 and WiDr), which produce only mutant p53 proteins with different mutation sites. Treatment of 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 SW620 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 oligonucleotide also inhibited the growth of three human normal cell lines (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 accumulated 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.
Hirota
Y
Y
New Product Research Laboratories IV, Daiichi Pharmaceutical Co., Ltd., Tokyo.
Horiuchi
T
T
Akahane
K
K
D001483:Base Sequence; D002455:Cell Division; D003110:Colonic Neoplasms / Q000473:pathology / Q000517:prevention & control*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D006801:Humans; D007082:Ileum / Q000166:cytology; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D012334:RNA, Neoplasm / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D004273:DNA, Neoplasm; D016376:Oligonucleotides, Antisense; D012334:RNA, Neoplasm; D016159:Tumor Suppressor Protein p53