위암세포주에서 Recombinant Human Interferon-r와 Adriamycin의 투여순서가 항암효과에 미치는 영향 = Effects of Combination Timing of Recombinant Human Interferon-r and Adriamycin on Cytotoxicity to Human Stomach Cancer Cells

다국어 초록 (Multilingual Abstract)

Numerous previous studies, both in vitro and in vivo, have demonstrated that the cytotoxicity can be enhanced by the combination of chemotherapeutic agent and interferons(IFNs) in various types of cancer cells. We have previously reported that combined treatment of MKN-45, human gastric adenocarcinoma cells, with adriamycin(ADM) and recombinant human interferon-r(rh-IFN-r) increased in the cytotoxicity. In this study, the effects of combination timing of rh-IFN-r and ADM on the cytotoxicity against MKN-45 were investigated using MTT assay. MKN-45 was treated with rh-IFN-r and ADM in vitro on three schedules : Treat A ; rh-IFN-r and ADM were treated simultaneously, Treat B ; rh-IFN-r was treated 24 hours after the treatment with ADM, Treat C ; rh-IFN-r was treated for 72 hours and followed by the treatment with ADM. The survival of MKN -45 was inhibited by ADM dose-dependently. 102 and 103U/ml of rh-IFN-r significantly inhibited the survival of MKN-45(% survival : 35.1 ±-1.2% and 34.4 ±1.1% in Treat A and 42.5 ± 2.1% and 45.9-±2.5% in Treat C, respectively). However no difference in the survival was observed between 102 and 103U/ml of rh-IFN-r. Combined treatment with rh-IFN-r and ADM significantly augmented the cytotoxicity at low concentrations of ADM. Combined effects of rh-IFN-r and ADM were evaluated using IC30(,ag/ml) to ADM. IC30s of MKN-45 in Treat A, B and C at 102 U/ml of rh -IFN-r _ were 0.019 -?- 0.003, 0.045 :I:0.001 and 0.054 ± 0.012, respectively, while IC30 of MKN-45 treated with ADM alone was 0.052±0.004. IC30s of MKN-45 in ADM alone group, Treat A, Treat B and Treat C at 103U/ml of rh-IFN-r were 0.047 ±0.003, 0.004 -±0.001, 0.031 ±0.004 and 0.056
0.008, respectively. These results indicate IC30s of Treat A and B were significantly lower than those of ADM alone(p<0.05) and IC30s of Treat A was significantly lower than those of Treat B(p <0.01). IC30s of Treat C, however, were not different from those of ADM alone. From these results demonstrating that cytotoxic effects were increased by the combination of rh-IFN-r and ADM in the order, Treat A > Treat B> Treat C, it can be concluded that the simultaneous administration of rh-IFN-r and ADM may be the most effective method to combine these two therapeutic modalties.