期刊
INFLAMMATORY BOWEL DISEASES
卷 25, 期 7, 页码 1187-1195出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/ibd/izz007
关键词
colitis-associated carcinogenesis; silibinin; Cdc25c; cell cycle arrest; animal model
资金
- National Key research and development program of the Ministry of Science and Technology of China [2016YFC0905301]
- National Nature Science Foundation of China [81472560, 81672451, 81672891]
- CAMS Innovation Fund for Medical Sciences (CIFMS) [2016-I2M-1-001, 2017-I2M-1-006]
Purpose Silibinin possesses the efficacy of anticancer and anti-inflammation. We aimed to test whether silibinin could prevent colitis-associated carcinogenesis in mouse model. Experimental Design Azoxymethane (AOM) and dextran sulfate sodium (DSS) were used to induce colitis-associated tumorigenesis in C57BL mice. Six-to-eight-week-old male mice were gavaged with 350 or 750 mg/kg of silibinin for 10 weeks right after DSS administration. The mice were then sacrificed, and colon tissues were measured for tumor multiplicity and size. Molecular changes about proliferation, apoptosis and inflammation were tested. Results Silibinin feeding showed a dose-dependent inhibition on the size of tumor induced by AOM/DSS in mice. In addition, silibinin inhibited cell proliferation evidenced by a decrease (P < 0.05) in Ki-67 and proliferating cell nuclear antigen (PCNA). However, silibinin did not show any significant effect on inflammation, apoptosis, and the mRNA expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and vascular endothelial growth factor (VEGF). The experiments in vitro showed that silibinin induced cell cycle arrest at G2/M phase in CT-26 cells, a mouse colonic cancer cell line. Furthermore, silibinin reduced the expression of Cdc25C and blocked the dephosphorylation of CDK1 at multiple sites both in vitro and in vivo. Conclusions Silibinin targets Cdc25C/CDK1 pathway and mitigates colitis-associated tumorigenesis in mice. Thus, our findings indicate the chemopreventive potential of silibinin for inflammation-associated colon cancer.
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