PT  - JOURNAL ARTICLE
AU  - YUKI SUEHIRO
AU  - YOSHIHIRO TAKEMOTO
AU  - ARATA NISHIMOTO
AU  - KOJI UENO
AU  - BUNGO SHIRASAWA
AU  - TOSHIKI TANAKA
AU  - NARUJI KUGIMIYA
AU  - ATSUSHI SUGA
AU  - EIJIRO HARADA
AU  - KIMIKAZU HAMANO
TI  - Dclk1 Inhibition Cancels 5-FU-induced Cell-cycle Arrest and Decreases Cell Survival in Colorectal Cancer
AID  - 10.21873/anticanres.12977
DP  - 2018 Nov 01
TA  - Anticancer Research
PG  - 6225--6230
VI  - 38
IP  - 11
4099  - http://ar.iiarjournals.org/content/38/11/6225.short
4100  - http://ar.iiarjournals.org/content/38/11/6225.full
SO  - Anticancer Res2018 Nov 01; 38
AB  - 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.