期刊
ANTICANCER RESEARCH
卷 38, 期 7, 页码 4247-4256出版社
INT INST ANTICANCER RESEARCH
DOI: 10.21873/anticanres.12721
关键词
Colorectal cancer; KRAS; 3D floating culture; nucleoside analogue; 5-bromouridine (BrUrd); 4-Amino-1-(beta-D-arabinofuranosyl)-2(1H)-pyridinone(3-deaza cytarabine)
类别
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan
Background/Aim: During screening for compounds that selectively suppress growth of human colorectal cancer (CRC) spheroids with mutant (mt) KRAS, the uridine analogue, 5-bromouridine (BrUrd) was identified and its derivatives were explored. Materials and Methods: DNA incorporation in two-dimensional (2D) and three-dimensional floating (3DF) cultures was examined with the uridine analogue, 5-ethynyl-2'-deoxyuridine (EdU). The area of HKe3 CRC spheroids expressing wild type (wt) KRAS (HKe3-wtKRAS) and mtKRAS (HKe3-mtKRAS) were measured in 3DF culture with 11 BrUrd derivatives. Results: EdU was strongly incorporated into newly-synthesized DNA from HKe3-mtKRAS cells compared to HKe3-wtKRAS in 2D and 3DF culture. 3-Deaza-cytarabine, which has properties of BrUrd and cytidine, was the most effective inhibitor of HKe3-mtKRAS spheroids with the least toxicity to HKe3-wtKRAS. Growth suppression of 3-deazacytarabine was stronger than cytarabine in 2D culture, and toxicity was lower than gemcitabine in long-term 3DF culture. Conclusion: 3-Deaza-cytarabine exhibits properties useful for the treatment of CRC patients with mtKRAS.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据