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A Preliminary Study on Enhancing the Efficacy of Sorafenib by Silencing STAT3 Gene in SK-Hep1 Cells |
Lin-na XIE1,2,Yan-hua ZENG2,Huo-zhao KE1,Wen-sheng HE1,Min ZHENG2,De-xin LIN2*() |
1 Department of Food and Bioengineering, Fujian Vocational College of Bioengineering,Fuzhou 350003, China 2 College of Basic Medical Sciences,Fujian Medical University, Fuzhou 350108, China |
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Abstract Objective:To determine the effect of STAT3 on sorafenib resistance in hepatocarcinoma cell SK-Hep1, and the role of STAT3 gene silencing on enhancing the efficacy of sorafenib in liver cancer. Methods:STAT3 gene was knocked down by short hairpin RNA based gene-silencing technology in SK-Hep1 cells. The cell proliferation and the sensitivity to sorafenib were detected by CCK8 assay. The expression levels of STAT3, p-STAT3(Y705),p-STAT3(S727)and its downstream proteins were detected by Western blot. Results:STAT3 knockdown cell line SK-Hep1-shSTAT3 was successfully constructed. In these cells, the level of STAT3 expression was decreased; the cell proliferation was significantly suppressed.Sorafenib treatment reduced the level of STAT3 phosphorylation and its downstream protein CyclinD1 and Mcl-1.Sorafenib resistance was reduced in STAT3 knockdown cells. Conclusion:Silencing STAT3 by RNA interference can significantly suppress SK-Hep1 cell proliferation, and enhance the sensitivity of liver cancer cells to sorafenib.The data indicates that STAT3 knockdown might be a new way to improve the efficacy of sorafenibin liver cancer.
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Received: 18 August 2017
Published: 16 December 2017
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