Wnt信号通路
下调和上调
结直肠癌
癌症研究
化学
佐剂
药理学
信号转导
癌症
医学
内科学
生物化学
基因
作者
Peng Yang,Wen Li,Rong Fu,Guo-Bin Ding,Saima Amin,Zhuoyu Li
标识
DOI:10.1021/acs.jafc.0c05551
摘要
Chemoresistance and toxicity are the main obstacles that limit the efficacy of 5-fluorouracil (5-FU) in colorectal cancer (CRC) therapy. Hence, it is urgent to identify new adjuvants that can sensitize CRC cells to conventional chemotherapeutic approaches. Cucurbitacin E (CE) is a natural triterpenoid, widely distributed in dietary plants, and shows antitumor effects. Here, we report that CE enhances the sensitivity of CRC cells to chemotherapy via attenuating the expression of adenosine 5'-triphosphate (ATP)-binding cassette transporters ABCC1 and MDR1. Combined with CE-functionalized magnetite nanoparticles and gene ontology analysis, we found that CE-binding proteins may involve Wnt/β-catenin signaling. To validate the findings, β-catenin was upregulated in drug-resistant cell lines, and the synergistic effects of CE and chemotherapeutics were accompanied by the downregulation of β-catenin. Moreover, TFAP4 was identified as an intracellular target of CE. Remarkably, the combination of CE and 5-FU treatment attenuated β-catenin, MDR1, and ABCC1 expressions, while TFAP4 overexpression reversed their expressions by 2.68 ± 0.46-, 0.72 ± 0.44-, and 0.93 ± 0.21-fold, respectively. Thus, our results indicate that CE sensitizes CRC cells to chemotherapy by decreasing the TFAP4/Wnt/β-catenin signaling, suggesting that the dietary compound CE can be used as a chemosensitizing adjuvant for CRC treatment.
科研通智能强力驱动
Strongly Powered by AbleSci AI