期刊
ONCOTARGET
卷 8, 期 5, 页码 8574-8589出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.14351
关键词
colorectal cancer; FOXM1; 5-FU; chemoresistance
资金
- National Natural Science Foundation of China [81272394, 81572457]
5-Fluorouracil (5-FU) is the most commonly used chemotherapeutic agent for colorectal cancer (CRC). However, frequently occurred 5-FU resistance poses a great challenge in the clinic. Elucidating the underlying mechanisms and developing effective strategies against 5-FU resistance are highly desired. Here we identified the upregulation of FOXM1 in 5-FU nonresponsive CRC patients by gene expression profile analysis and 5-FU-resistant CRC cells by qRT-PCR assay. Silencing of FOXM1 promoted the sensitivity of CRC cells to 5-FU by enhancing cell apoptosis, while overexpression of FOXM1 conferred CRC cells with 5-FU resistance both in vitro and in vivo. Furthermore, we showed that genetic and pharmacological inhibition of FOXM1 resensitized resistant CRC cells to 5-FU treatment. Mechanistically, FOXM1 promoted the transcription of ABCC10 by directly binding to its promoter region. Notably, treatment with ABCC10 inhibitor reversed FOXM1-induced resistance to 5-FU in vivo. Clinical investigation revealed that the levels of FOXM1 and ABCC10 were positively correlated in CRC tissues. Therefore, FOXM1 promotes 5-FU resistance by upregulating ABCC10, suggesting that FOXM1/ABCC10 axis may serve as a potential therapeutic target for 5-FU resistance in CRC patients.
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