Twelfth People s Hospital of Guangzhou Municipal

Guangzhou, China

Twelfth People s Hospital of Guangzhou Municipal

Guangzhou, China

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Yuxian H.,Southern Medical University | Xintong C.,Mount Sinai School of Medicine | Xia L.,Twelfth People s Hospital of Guangzhou Municipal | Guanyang W.,Southern Medical University | And 4 more authors.
Chinese Journal of Cancer Biotherapy | Year: 2015

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-kB inhibitor JSH-23 decreased the expressions of NKG2DLs in HepG2 cells, the agonist of NF-kB 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-kB pathway. © 2015, Editorial office of Chinese Journal of Cancer Biotherapy. All rights reserved.

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