論文 - 詳細
| RRC ID | 43446 |
|---|---|
| 著者 | Tozawa K, Oshima T, Kobayashi T, Yamamoto N, Hayashi C, Matsumoto T, Miwa H. |
| タイトル | Oxaliplatin in treatment of the cisplatin-resistant MKN45 cell line of gastric cancer. |
| ジャーナル | Anticancer Res |
| Abstract |
BACKGROUND AND AIM:The clinical efficiency of cisplatin (CDDP) against gastric cancer is often limited by the development of resistance. A third-generation platinum-containing agent, oxaliplatin (L-OHP), has been introduced for treating gastric cancer. Here, we studied oxaliplatin in vitro to reveal the mechanism of acquiring drug resistance and whether a cisplatin-resistant gastric cancer cell line has susceptibility to oxaliplatin. MATERIALS AND METHODS:A cisplatin-resistant gastric cancer cell line (MKN45/CDDP/ R1) was established by continuous exposure of MKN45 cells to cisplatin. The amount of excision repair cross-complementation group 1 (ERCC1) and glutathione-S-transferase (GST)-pi mRNA was measured by real-time polymerase chain reaction (PCR). To examine the chemosensitivity to CDDP and L-OHP in MKN45 and MKN45/CDDP/R1 cells, a collagen gel droplet-embedded culture drug sensitivity test (CD-DST) was performed. The intracellular concentration of CDDP and L-OHP were also measured to see if the drugs would be taken up by these cell lines. RESULTS:The MKN45/CDDP/R1 cell line was resistant to CDDP. The ERCC1 and GST-pi mRNA was significantly increased in MKN45/CDDP/R1 cells, indicating that the cells acquired resistance to CDDP. Intracellular CDDP was not detected in MKN45/CDDP/R1 cells up to 48 h after incubation, indicating that uptake and efflux processes of CDDP were altered in these cells. MKN45/CDDP/R1 cells were still susceptible to L-OHP. The intracellular concentration of CDDP but not L-OHP was significantly reduced in MKN45/CDDP/R1 cells. CONCLUSION:We established a CDDP-resistant cell line using MKN45 cells, in which ERCC1 and GST-pi were increased. This cell line showed susceptibility to the new generation platinum agent L-OHP, suggesting this anticancer agent could be used in second-line treatment of patients with CDDP-resistant gastric neoplasms. |
| 巻・号 | 28(4B) |
| ページ | 2087-92 |
| 公開日 | 2008-1-1 |
| PMID | 18751380 |
| MeSH | Adenocarcinoma / drug therapy* Adenocarcinoma / genetics Adenocarcinoma / metabolism Antineoplastic Agents / pharmacokinetics Antineoplastic Agents / pharmacology* Cell Line, Tumor Cisplatin / pharmacokinetics Cisplatin / pharmacology* DNA-Binding Proteins / biosynthesis DNA-Binding Proteins / genetics Drug Resistance, Neoplasm Endonucleases / biosynthesis Endonucleases / genetics Glutathione S-Transferase pi / biosynthesis Glutathione S-Transferase pi / genetics Humans Organoplatinum Compounds / pharmacokinetics Organoplatinum Compounds / pharmacology* Oxaliplatin RNA, Messenger / biosynthesis RNA, Messenger / genetics Stomach Neoplasms / drug therapy* Stomach Neoplasms / genetics Stomach Neoplasms / metabolism |
| IF | 1.994 |
| 引用数 | 14 |
| WOS 分野 | ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | |