氟尿嘧啶
体内
癌症研究
下调和上调
体外
结直肠癌
化疗
癌症
医学
生物
化学
内科学
基因
生物化学
生物技术
作者
Lili Deng,Yan Zhao,Wen Liu
标识
DOI:10.1080/1120009x.2023.2288742
摘要
As a long-established chemotherapy drug, 5-fluorouracil (5-FU) is widely used to clinically manage colorectal cancer (CRC). However, a substantial portion of patients develop 5-FU resistance at some stage, which poses a great challenge. Therefore, revealing the mechanisms that could guide the development of effective strategies to overcome 5-FU resistance is required. Here, we report that the expression of PFKP was higher in HCT116/5-FU CRC. Furthermore, genetic suppression of PFKP suppresses glycolysis, NF-κB activation, and expression of GLUT1 and HK2 in HCT116/5-FU cells. PFKP overexpression promotes glycolysis and expression of GLUT1 and HK2 via the NF-κB signaling pathway in HCT116 cells. Our functional assays demonstrated that PFKP silencing could sensitize HCT116/5-FU cells to 5-FU with an elevated population of apoptotic cells. In contrast, forced expression of PFKP conferred 5-FU resistance in HCT116 cells. Furthermore, PFKP silencing significantly inhibited CRC xenograft tumor growth. Notably, the combination of PFKP silencing and 5-FU inhibited tumor growth. Therefore, our results demonstrated that PFKP enhances 5-FU resistance by promoting glycolysis, indicating that PFKP could be a novel candidate for targeted therapy for 5-FU-resistant CRC.
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