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Archive > Volume 22 Issue 6 > 2015,22(6):703-709. DOI:10.3872/j.issn.1007-385X.2015.06.005 Prev Next
Monographic Report
Sunitinib induces the expressions of NKG2DLs on human hepatocellular carcinoma HepG2 cells by activating alternative NF-κB pathway
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Abstract:
Objective:To investigate molecular mechanism of sunitinib-induced expressions of natural killer group 2 member D ligands (NKG2DLs) in human hepatocellular carcinoma cell HepG2.Methods: HepG2 cells were cultivated by routine method. DNA damage in HepG2 cells was detected by single cell gel electrophoresis (SCGE) assay. The expressions of DNA damage-related molecule were quantitated by RT-qPCR. The levels of NKG2DLs, IKKα and IkBα were determined by immunoblotting. Results: Single cell gel electrophoresis revealed that HepG2 cells have various degree of DNA damages after exposed to sunitinib. RT-qPCR analysis showed that the expressions of AP-1, ATM, and ATR mRNA in HepG2 cells treated with sunitinib were significantly increased, whereas the levels of CHK1，CHK2，GSK3β mRNA were markedly lower. While the NF-κB inhibitor JSH-23 decreased the expressions of NKG2DLs in HepG2 cells, the agonist of NF-κB increased the expressions of these molecules. Furthermore, in HepG2 treated with sunitinib, IKKα was phosphorylated, and IkBα was activated. Conclusion: The data indicated that sunitinib induces the upregulated expressions of NKG2DLs in carcinoma cells by DNA damage-related molecules with activate the NF-κB pathway.
Keywords:
sunitinib ; hepatocellular carcinoma ; DNA damage repair signal molecule ; HepG2 cell ; NF-κB gene family member
Project Supported:
Project supported by the National Natural Science Foundation for Young Scientists of China (No. 81302372，81300431), and the Excellent Middle and Yong Aged Experts Project of Zhujiang Hospital Southern Medical University (No.201207008)
