期刊
CANCER BIOLOGY & THERAPY
卷 19, 期 11, 页码 1057-1064出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15384047.2018.1480280
关键词
HCC; sorafenib; caspase-1; LPS
类别
资金
- National Natural Science Foundation of China [81670566]
- Jiangsu Province's Key Provincial Talents Program [ZDRCA2016066]
Sorafenib has been demonstrated to be a beneficial treatment for advanced hepatocellular carcinoma (HCC). Emerging evidence indicates that caspase-1 activation plays a crucial role in HCC progression. However, the relationship between caspase-1 and sorafenib has rarely been reported. In this study, we showed that caspase-1 was essential for lipopolysaccharide (LPS)-induced epithelial-mesenchymal transition (EMT). Moreover, sorafenib treatment could inhibit LPS-stimulated caspase-1 overexpression through restricting the nuclear transport of p65, which contributed to inactivation of NF-kappa B. Co-immunoprecipitation (Co-IP) experiments and immunoblot analysis indicated that sorafenib treatment decreased the SUMOylation of p65 via inhibiting TLR4/stat3/SUMO1 signaling cascades. In conclusion, the results of this study suggest that sorafenib inhibits caspase-1 expression through suppressing the nuclear translocation of p65 and provide new insights into the mechanisms of sorafenib treatment in HCC.
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