ANTIPROLIFERATIVE EFFECTS OF UNMODIFIED ANTISENSE OLIGODEOXYNUCLEOTIDES TARGETED AGAINST C-RAF MESSENGER-RNA - USE OF POLY (LYSINE SERINE) COPOLYMERS OR CATIONIC LIPOPOLYAMINES/

1, It is now known that nuclease-resistant phosphorothioate antisense oligodeoxynucleotides (ODN) have some actions that are unrelated to an tisense mechanisms. In the present study we assessed the anti-prolifer ative effects of phosphorothioate (PS) and phosphodiester (PO; unmodif ied) antisense ODN targeted against c-raf mRNA on pancreatic cancer ce lls in vitro, using poly (lysine/serine) copolymers conjugated with po lyethylene glycol (PLSP) or cationic lipopolyamines (Transfectam) as c arriers. 2, The anti-proliferative effect of the PO antisense ODN was significantly (P<0.05) greater than that of the PS ODN, either complex ed with PLSP (2 mu mol/L ODN) or the Transfectam (0.5 mu mol/L ODN), H owever, the effect of the PS or PO antisense ODN was not dependent on the antisense sequence. The c-raf mRNA levels, assessed by reverse tra nscription-polymerase chain reaction, were obviously reduced by both P O and PS antisense ODN compared with mismatched ODN when complexed wit h the Transfectam (1 mu mol/L ODN), 3, Although the anti-proliferative effects were mainly unrelated to antisense mechanisms, unmodified ant isense ODN complexed with some carriers could be used as anti-tumour a gents considering that synthetic carriers can be modified to improve f unctions, such as delivery.