論文 - 詳細
| RRC ID | 54713 |
|---|---|
| 著者 | Suehiro Y, Takemoto Y, Nishimoto A, Ueno K, Shirasawa B, Tanaka T, Kugimiya N, Suga A, Harada E, Hamano K. |
| タイトル | Dclk1 Inhibition Cancels 5-FU-induced Cell-cycle Arrest and Decreases Cell Survival in Colorectal Cancer. |
| ジャーナル | Anticancer Res |
| Abstract |
BACKGROUND/AIM:5-Fluorouracil (5-FU) is frequently used in colorectal cancer treatment, but with limited success. The aim of the present study was to explore the cytotoxic effects of 5-FU, in combination with inhibition of doublecortin-like kinase 1 (Dclk1), a tumor stem cell marker that regulates pro-survival signaling in colorectal cancer cells, in the human colon cancer cell line, COLO-320. MATERIALS AND METHODS:The effects of 5-FU treatment plus Dclk1 inhibition on the phosphorylation of checkpoint kinase 1 (Chk1), cell cycle, DNA damage, apoptosis, and cell survival in COLO-320 cells were evaluated. RESULTS:Combined treatment with 5-FU and a Dclk1 inhibitor, LRRK2-IN-1 (LRRK), decreased 5-FU-induced phosphorylation of Chk1 and canceled 5-FU-induced cell-cycle arrest at the S phase. Combined treatment with 5-FU and LRRK failed to induce poly (ADP-ribose) polymerase 1 (PARP-1) cleavage, but tended to decrease cell survival compared to individual treatment with 5-FU or LRRK. CONCLUSION:These results indicate that a combination of 5-FU and LRRK may be an effective, novel approach for colorectal cancer therapy. |
| 巻・号 | 38(11) |
| ページ | 6225-6230 |
| 公開日 | 2018-11-1 |
| DOI | 10.21873/anticanres.12977 |
| PII | 38/11/6225 |
| PMID | 30396941 |
| MeSH | Benzodiazepinones / pharmacology* Cell Cycle Checkpoints Cell Line, Tumor Cell Proliferation / drug effects Cell Survival / drug effects Checkpoint Kinase 1 / metabolism* Colonic Neoplasms / drug therapy Colonic Neoplasms / metabolism* Drug Synergism Fluorouracil / pharmacology* Gene Expression Regulation, Neoplastic / drug effects Humans Phosphorylation / drug effects Poly (ADP-Ribose) Polymerase-1 / metabolism* Pyrimidines / pharmacology* Signal Transduction / drug effects |
| IF | 1.935 |
| 引用数 | 5 |
| リソース情報 | |
| ヒト・動物細胞 | COLO-320(RCB1193) |