論文 - 詳細
| RRC ID | 69334 |
|---|---|
| 著者 | Nakamura A, Nakajima G, Okuyama R, Kuramochi H, Kondoh Y, Kanemura T, Takechi T, Yamamoto M, Hayashi K. |
| タイトル | Enhancement of 5-fluorouracil-induced cytotoxicity by leucovorin in 5-fluorouracil-resistant gastric cancer cells with upregulated expression of thymidylate synthase. |
| ジャーナル | Gastric Cancer |
| Abstract |
BACKGROUND:Elucidation of the mechanisms by which gastric cancer cells acquire resistance to 5-fluorouracil (5FU) may provide important clues to the development of effective chemotherapy for 5FU-resistant gastric cancer METHODS:Four 5FU-resistant cell lines (MKN45/5FU, MKN74/5FU, NCI-N87/5FU, and KATOIII/5FU) were established by continuous exposure of the cells to progressively increasing concentrations of 5FU for about 1 year. Then, mRNA expression levels of four genes associated with 5FU metabolism, i.e., thymidylate synthase (TS), dihydropyrimidine dehydrogenase, thymidine phosphorylase, and orotate phosphoribosyltransferase, were quantitatively evaluated by real-time reverse transcriptase-polymerase chain reaction. In addition, TS protein expression was measured by Western blot analysis. RESULTS:As compared with the parent cell lines, the 5FU-resistant cell lines showed 3.8- to 11.6-fold higher resistance to 5FU, as well as 1.9- to 3.5-fold higher TS mRNA expression and 1.6- to 7.1-fold higher TS protein expression. In contrast, the expressions of other genes did not differ significantly among the cell lines. The cytotoxicity of 5FU was enhanced 2.3- to 2.8 fold by leucovorin (LV) against three of the four 5FU-resistant cell lines. CONCLUSIONS:Collectively, LV enhanced the cytotoxicity of 5FU not only against the parent gastric cancer cell lines, but also against the 5FU-resistant cell lines, even those with elevated TS expression levels. These results suggest that clinical studies of a combination of 5FU and LV are warranted in patients who have recurrent gastric cancer after 5FU-based therapy. |
| 巻・号 | 17(1) |
| ページ | 188-95 |
| 公開日 | 2014-1-1 |
| DOI | 10.1007/s10120-013-0249-7 |
| PMID | 23494117 |
| PMC | PMC3889291 |
| MeSH | Cell Line, Tumor Drug Resistance, Neoplasm / drug effects* Fluorouracil / pharmacology* Gene Expression Regulation, Neoplastic / drug effects Humans Leucovorin / pharmacology* Stomach Neoplasms / drug therapy* Stomach Neoplasms / genetics Stomach Neoplasms / metabolism Thymidylate Synthase / genetics Thymidylate Synthase / metabolism* Up-Regulation / drug effects |
| IF | 7.088 |
| リソース情報 | |
| ヒト・動物細胞 | MKN74(RCB1002) Kato III(RCB2088) |