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Sorafenib inhibits 5-fluorouracil-resistant gastric cancer cell growth.

Authors
 Hee Man Kim  ;  Sun A Kim  ;  Soo Been Park  ;  Jae Hee Cho  ;  Si Young Song 
Citation
 SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, Vol.52(5) : 577-584, 2017 
Journal Title
 SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY 
ISSN
 0036-5521 
Issue Date
2017
MeSH
Animals ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage* ; Apoptosis ; Caspase 3/metabolism ; Cell Cycle/drug effects ; Cell Line, Tumor ; Cell Proliferation ; Drug Resistance, Neoplasm ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Female ; Fluorouracil/administration & dosage* ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Niacinamide/administration & dosage ; Niacinamide/analogs & derivatives* ; Phenylurea Compounds/administration & dosage* ; Stomach/pathology ; Stomach Neoplasms/drug therapy* ; Stomach Neoplasms/pathology ; Xenograft Model Antitumor Assays
Keywords
5-fluorouracil ; Gastric cancer ; drug resistance ; neoplastic stem cell ; sorafenib ; sphere formation
Abstract
BACKGROUND: Sorafenib is a multi-kinase inhibitor used in the treatment of various cancers. This study investigated the inhibitory effect of sorafenib on xenograft models of gastric cancer cells and 5-fluorouracil (5-FU)-resistant cells. METHODS: The half-maximal inhibitory concentration (IC50) of sorafenib in NCI-N87 cells was determined. Xenograft models were established using BALB/c nude mice and were divided into four groups treated with vehicle, sorafenib (20 mg kg-1 day-1), 5-FU (50 mg kg-1 week-1), or a combination of sorafenib (20 mg kg-1 day-1) plus 5-FU (50 mg kg-1 week-1). 5-FU-resistant NCI-N87 cells were established by repeated exposure to 5-FU. RESULTS: Sorafenib inhibited NCI-N87 cell growth in a concentration-dependent manner with a mean IC50 of 16.345 ± 5.391 μM. Phosphorylation levels of mitogen-activated protein kinase kinase and extracellular signal-regulated kinase in these cells decreased in a dose-dependent manner after exposure to sorafenib. Sorafenib induced the activation of caspase-3, and its combination with 5-FU more effectively inhibited the growth of xenograft tumors than either sorafenib or 5-FU alone (p < 0.05). Sorafenib markedly inhibited 5-FU-resistant NCI-N87 cell growth as well as sphere formation in both parental and 5-FU-resistant NCI-N87 cells. CONCLUSIONS: The sorafenib and 5-FU combination exhibited enhanced antitumor effects in a gastric cancer xenograft model and inhibited 5-FU-resistant cell proliferation and sphere formation. These findings suggest that sorafenib is useful in overcoming gastric cancer resistance to conventional chemotherapy.
Full Text
http://www.tandfonline.com/doi/full/10.1080/00365521.2017.1278786
DOI
10.1080/00365521.2017.1278786
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Sun A(김선아) ORCID logo https://orcid.org/0000-0002-7174-3640
Song, Si Young(송시영) ORCID logo https://orcid.org/0000-0002-1417-4314
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/154711
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