論文 - 詳細
| RRC ID | 42599 |
|---|---|
| 著者 | Miyazaki K, Shibahara T, Sato D, Uchida K, Suzuki H, Matsui H, Yanaka A, Nakahara A, Matsuzaki Y. |
| タイトル | Influence of chemotherapeutic agents and cytokines on the expression of 5-fluorouracil-associated enzymes in human colon cancer cell lines. |
| ジャーナル | J Gastroenterol |
| Abstract |
BACKGROUND:Several studies have demonstrated that intratumoral expression of catabolizing and anabolizing enzymes for 5-fluorouracil (5-FU) is important in the response of cancers to 5-FU-based chemotherapy. We investigated the influence of other chemotherapeutic agents or cytokines, which are often administered for enhancing the efficacy of 5-FU, on the tumoral expression of 5-FU-associated enzymes, i.e., dihydropyrimidine dehydrogenase (DPD), thymidylate synthase (TS), orotate phosphoribosyl transferase (OPRT), and thymidine phosphorylase (TP). METHODS:Human colon cancer cell lines (HT-29, Caco-2, and DLD-1) were incubated with 5-FU and with 5-FU combined with cisplatin, camptothecin, paclitaxel, mitomycin C, interferon, or TNF-related apoptosis-inducing ligand. mRNA expression of 5-FU-associated enzymes was assessed by real-time PCR. Activity of each enzyme and intracellular 5-FU accumulation after incubation with such agents were also evaluated. RESULTS:Each agent had a synergistic effect on the cytotoxicity of 5-FU. All chemotherapeutic agents other than cytokines induced marked alteration of the mRNA expression profile of 5-FU-associated enzymes; depression of DPD, elevation of TS, and slight suppression of OPRT and TP. In accordance with mRNA expression, enzyme activity of DPD was significantly depressed by such agents. Furthermore, although 5-FU itself increased DPD mRNA expression, a mechanism considered to be related to the acquisition of 5-FU resistance, the addition of cisplatin or camptothecin significantly inhibited the 5-FU-induced elevation of DPD. CONCLUSIONS:5-FU-associated enzymes in colon cancer cells were greatly influenced by various chemotherapeutic agents; in particular, DPD expression was depressed. These results appear important in planning chemotherapy and also in understanding the development of adverse effects of 5-FU. |
| 巻・号 | 41(2) |
| ページ | 140-50 |
| 公開日 | 2006-2-1 |
| DOI | 10.1007/s00535-005-1733-6 |
| PMID | 16568373 |
| MeSH | Antimetabolites, Antineoplastic / pharmacology* Apoptosis Caco-2 Cells Camptothecin / pharmacology Cell Line, Tumor Cisplatin / pharmacology Colonic Neoplasms / enzymology* Cytokines / pharmacology* Dihydrouracil Dehydrogenase (NADP) / metabolism Fluorouracil / metabolism* Fluorouracil / pharmacology* HT29 Cells Humans Interferons / pharmacology Ligands Mitomycin / pharmacology Orotate Phosphoribosyltransferase / metabolism Paclitaxel / pharmacology RNA, Messenger / analysis Thymidine Phosphorylase / metabolism Thymidylate Synthase / metabolism |
| IF | 6.132 |
| 引用数 | 23 |
| WOS 分野 | GASTROENTEROLOGY & HEPATOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | CACO-2(RCB0988) |