期刊
INTERNATIONAL JOURNAL OF ONCOLOGY
卷 51, 期 6, 页码 1775-1784出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2017.4159
关键词
cancer stem cells; BC-02; tumor spheres; chemoresistance; CD13; ROS
类别
资金
- National Natural Science Foundation of China [81503108, 81373282, 81201262, 81471048]
- Shandong Province Higher Educational Science and Technology Program [J15LM58]
- Research Award Fund for Outstanding Young and Middle-aged Scientists of Shandong Province [BS2015YY016]
Cancer stem cells (CSCs) are responsible for chemoresistance, tumor recurrence and metastasis. Reportedly, aminopeptidase N (APN, also known as CD13) is a marker for semi-quiescent CSCs and a therapeutic target in human liver CSCs. In the present study, the effect of BC-02, a compound obtained by conjugating a CD13 inhibitor bestatin and fluorouracil (5-FU), was investigated toward liver CSCs. Tumor spheres formed in serum-free culture conditions have been successfully used to enrich CSCs. In this study, the sphere cells were shown to have several characteristics of CSCs, including drug resistance, high tumorigenicity, epithelial-mesenchymal transition (EMT) phenotype, lower reactive oxygen species (ROS) levels, greater colony-forming efficiency and increased proliferation capacity in vitro. Furthermore, BC-02 effectively suppressed self-renewal and malignant proliferation of CSCs compared with 5-FU, bestatin, and even the combination of 5-FU and bestatin. In addition, cell proliferation was effectively suppressed when exposed to 5-FU plus CD13-neutralizing antibody (CD13 Ab) compared with 5-FU alone. BC-02 can effectively inhibit the activity of CD13. Results demonstrated that CD13 inhibitor BC-02 impaired the properties of liver CSCs by targeting CD13 and upregulating the intracellular ROS and ROS-induced DNA damage. BC-02 might be a potential therapeutic agent for eradicating the liver CSCs and overcoming chemoresistance in liver cancer.
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