ИСТИНА

The gene silencing mediated by small interfering RNA (siRNA) was used to increase a chemotherapy effect. The siRNA of 19-22 base pair long and small hairpin RNA (shRNA) produced from expression vector were used for this study. A number of colon tumor cell lines: Caco2, HT-29 and HCT-116 were tested for the cisplatin and oxalyplatin sensitivity. The HT-29 appeared to be more susceptible for oxalyplatin. The p53-negative HT-29 cells seem to escape from p53-depended apoptosis and anticancer platin based drugs activate caspase cascade. We performed serially repeated RNA silencing of caspase linked ingibitors of apoptosis (IAP). Mixed cocktail of anti-FLIP, IAP-2 shRNAs and antiIAP-5 (Survivin), HspA5 siRNAs showed twice stronger effect than oxalyplatin alone: 38 and 18% respectively. Combinations of IAP-2/FLIP and IAP-5 with oxalyplatin resulted in 50 to 60% apoptosis compared with 10% of the negative control. In summary, anti-FLIP and IAP-2 together with small doze oxalyplatin demonstrated the same apoptotic death of cells as treated with (3x)-oxalyplatin alone. Our data indicate that anti-IAP siRNA seem to be a prominent tool to increase the effect of standart chemotherapy and significantly reduce it‘s overload for cancer patients.