sorafenib의 5-fluorouracil내성을 획득한 위암세포주에 대한 억제효과와 sorafenib과 5-fluorouracil의 이종이식모델에 대한 병합효과에 대한 연구

Dept. of Medicine/박사Sorafenib is a multi-kinase inhibitor used for the targeted therapy against cancer. This study investigated the anti-tumor effect of sorafenib in combination with 5-fluorouracil (5-FU) in xenograft models produced using NCI-N87 cells, and tested the potential inhibitory effect of sorafenib on 5-FU-resistant NCI-N87 cells and sphere formation of NCI-N87 cells and 5-FU-resistant NCI-N87 cells. Sorafenib inhibited the growth of NCI-N87 cells in a dose-dependent manner; the mean IC50 of sorafenib was 16.345 ± 5.391 μM. After a 2-hour exposure to sorefenib, phosphorylation levels of MEK and ERK in NCI-N87 cells were reduced dose-dependently. Sorafenib induced the activation of caspase-3 in vitro and apoptosis in vivo. Xenograft mice were established by the subcutaneous implantation of NCI-N87 cells into BALB/c nude mice. To investigate the effect of a combination of sorafenib and 5-FU, four groups of xenograft mice were prepared: vehicle, sorafenib (20 mg/kg/day), 5-FU (50 mg/kg/week), and sorafenib (20 mg/kg/day) + 5-FU (50 mg/kg/week) were prepared. Sorafenib was administered orally once a day and 5-FU was injected intraperitoneally every week for 3 weeks. Sorafenib in combination with 5-FU significantly inhibited the growth of xenograft tumors compared to sorafenib alone or 5-FU alone (P