蟾毒灵通过靶向CPSF4抑制hTERT表达和结肠癌细胞生长。
Bufalin Inhibits hTERT Expression and Colorectal Cancer Cell Growth by Targeting CPSF4.
作者信息
Zhang Ningning, Xie Yunpeng, Tai Yidi, Gao Yingying, Guo Wei, Yu Wendan, Li Jia, Feng Xu, Hao Jiaojiao, Gao Yue, Zhao Xinrui, Liao Yina, Jiang Wei, Liu Ge, Deng Wuguo, Cui Xiaonan
机构信息
The First Affiliated Hospital & Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
出版信息
Cell Physiol Biochem. 2016;40(6):1559-1569. doi: 10.1159/000453206. Epub 2016 Dec 21.
BACKGROUND/AIMS: Bufalin can induce apoptosis in certain human cancer cell lines, but bufalin has not yet been thoroughly evaluated in colorectal cancer cells. Cleavage and polyadenylation specific factor 4 (CPSF4) and human telomerase reverse transcriptase (hTERT) play important roles in colorectal cancer growth. The aim of this study was to investigate the roles and interactions of bufalin, CPSF4 and hTERT and the effects of bufalin in human colorectal cancer.
METHODS
We treated LoVo and SW620 cells with bufalin to investigate the effect of bufalin on proliferation, apoptosis and migration. We verified the relationship between CPSF4 and hTERT using pulldown assays, luciferase reporter assays and chromatin immunoprecipitation (ChIP) assays.
RESULTS
Bufalin inhibited the proliferation and migration of and induced apoptosis in LoVo and SW620 cells. We identified CPSF4 as an hTERT promoter-binding protein in colorectal cancer cells.
CONCLUSION
Our study identified bufalin as a potential small molecule inhibitor for cancer therapy.
背景/目的：蟾毒灵可诱导某些人类癌细胞系发生凋亡，但尚未在结肠癌细胞中进行全面评估。切割和聚腺苷酸化特异性因子4（CPSF4）和人类端粒酶逆转录酶（hTERT）在结肠癌生长中起重要作用。本研究旨在探讨蟾毒灵、CPSF4和hTERT的作用及相互作用，以及蟾毒灵对人类结肠癌的影响。
方法
我们用蟾毒灵处理LoVo和SW620细胞，以研究蟾毒灵对增殖、凋亡和迁移的影响。我们使用下拉实验、荧光素酶报告基因实验和染色质免疫沉淀（ChIP）实验验证CPSF4和hTERT之间的关系。
结果
蟾毒灵抑制LoVo和SW620细胞的增殖和迁移，并诱导其凋亡。我们确定CPSF4是结肠癌细胞中hTERT启动子结合蛋白。
结论
我们的研究确定蟾毒灵是一种潜在的用于癌症治疗的小分子抑制剂。
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