Sorafenib inhibits caspase-1 expression through suppressing TLR4/stat3/SUMO1 pathway in hepatocellular carcinoma

ABSTRACT

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-κB. 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.

Keywords:

• HCC
• sorafenib
• caspase-1
• LPS

Disclosure of interest

None.

Supplementary material

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Additional information

Funding

This work was supported by grants from the National Natural Science Foundation of China (Grant No. 81670566), Jiangsu Province’s Key Provincial Talents Program (Grant No. ZDRCA2016066).