論文 - 詳細
| RRC ID | 42415 |
|---|---|
| 著者 | Toiyama Y, Tanaka K, Konishi N, Mohri Y, Tonouchi H, Miki C, Kusunoki M. |
| タイトル | Administration sequence-dependent antitumor effects of paclitaxel and 5-fluorouracil in the human gastric cancer cell line MKN45. |
| ジャーナル | Cancer Chemother Pharmacol |
| Abstract |
BACKGROUND:The clinical outcome of gastric cancer patients has been improved by combination of 5-fluorouracil (5-FU) and paclitaxel (PXL). However, the optimal schedule of this combination has not been determined. METHODS:The efficacies of sequential administrations of 5-FU and PXL on the gastric cancer cell line MKN45 were investigated using a WST-8 colorimetric assay. The cell cycle distribution of each drug was evaluated by flow-cytometry. Furthermore, the mechanism of antitumor activity enhancement by the administration sequence was investigated by western blotting. RESULTS:MKN45 cell growth was significantly inhibited by each drug in a dose- and time-dependent manner. The cytotoxicities of PXL followed by 5-FU were significantly greater than those of 5-FU followed by PXL. The flow-cytometric analysis revealed that PXL exposure caused viable cell accumulation in G2/M phase in a dose-dependent manner. Western blotting showed that PXL exposure followed by 5-FU up-regulated Chk1 and Wee1 protein expressions until PXL removal and 5-FU exposure, when these expressions gradually decreased to their basal levels. 14-3-3sigma protein expression was significantly up-regulated upon PXL treatment followed by 5-FU. Interestingly, Mad2 protein expression with PXL treatment followed by 5-FU gradually increased after the PXL removal and 5-FU exposure. CONCLUSIONS:PXL followed by 5-FU administration may be the optimal sequence for treatment of gastric cancer. The enhanced viable cell accumulation after PXL pretreatment may be related to G2 arrest. After PXL removal and 5-FU exposure, the cells progressing to M phase may undergo cell death by mitotic catastrophe due to DNA damage caused by 5-FU exposure. |
| 巻・号 | 57(3) |
| ページ | 368-75 |
| 公開日 | 2006-2-1 |
| DOI | 10.1007/s00280-005-0057-9 |
| PMID | 16075279 |
| MeSH | 14-3-3 Proteins / metabolism Antimetabolites, Antineoplastic / pharmacology Antineoplastic Agents, Phytogenic / pharmacology Blotting, Western Calcium-Binding Proteins / metabolism Cell Cycle Proteins / metabolism Cell Division / drug effects Cell Line, Tumor Cell Proliferation / drug effects Cell Survival / drug effects Checkpoint Kinase 1 Dose-Response Relationship, Drug Flow Cytometry / methods Fluorouracil / administration & dosage Fluorouracil / pharmacology* G2 Phase / drug effects Humans Mad2 Proteins Nuclear Proteins / metabolism Paclitaxel / administration & dosage Paclitaxel / pharmacology* Protein Kinases / metabolism Protein-Tyrosine Kinases / metabolism Repressor Proteins / metabolism Time Factors |
| IF | 2.967 |
| 引用数 | 8 |
| WOS 分野 | PHARMACOLOGY & PHARMACY ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | MKN45(RCB1001) |