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ANTI‐PROLIFERATIVE EFFECTS OF UNMODIFIED ANTISENSE OLIGODEOXYNUCLEOTIDES TARGETED AGAINST c‐raf mRNA: USE OF POLY (LYSINE/SERINE) COPOLYMERS OR CATIONIC LIPOPOLYAMINES
Author(s) -
Aoki Y.,
Kawa S.,
Karasawa Y.,
Horiuchi A.,
Kiyosawa K.
Publication year - 1998
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1998.tb02279.x
Subject(s) - phosphodiester bond , microbiology and biotechnology , in vitro , cpg oligodeoxynucleotide , chemistry , sense (electronics) , messenger rna , serine , antisense therapy , nuclease , biology , biochemistry , oligonucleotide , rna , gene expression , dna , phosphorylation , locked nucleic acid , gene , dna methylation
SUMMARY 1. It is now known that nuclease‐resistant phosphorothioate antisense oligodeoxynucleotides (ODN) have some actions that are unrelated to antisense mechanisms. In the present study we assessed the anti‐proliferative effects of phosphorothioate (PS) and phosphodiester (PO; unmodified) antisense ODN targeted against c‐ raf mRNA on pancreatic cancer cells in vitro, using poly (lysine/serine) copolymers conjugated with polyethylene glycol (PLSP) or cationic lipopolyamines (Transfectam) as carriers. 2. The anti‐proliferative effect of the PO antisense ODN was significantly ( P < 0.05) greater than that of the PS ODN, either complexed with PLSP (2 μmol/L ODN) or the Transfectam (0.5 μmol/L ODN). However, the effect of the PS or PO antisense ODN was not dependent on the antisense sequence. The c‐raf mRNA levels, assessed by reverse transcription‐polymerase chain reaction, were obviously reduced by both PO and PS anti‐sense ODN compared with mismatched ODN when complexed with the Transfectam (1 μmol/L ODN). 3. Although the anti‐proliferative effects were mainly unrelated to antisense mechanisms, unmodified antisense ODN complexed with some carriers could be used as anti‐tumour agents considering that synthetic carriers can be modified to improve functions, such as delivery.