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Chrysin inhibits sphere formation in SMMC-7721 cells via modulation of SHP-1/STAT3 signaling pathway

Authors Zhang Y, Chen F, Xiao X, Pan W, Yuan Q, Cao J

Received 6 November 2018

Accepted for publication 27 February 2019

Published 10 April 2019 Volume 2019:11 Pages 2977—2985

DOI https://doi.org/10.2147/CMAR.S193647

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Dr Antonella D'Anneo


Yanqin Zhang,1,2 Feng Chen,1 Xinghua Xiao,1 Weinan Pan,2 Qing Yuan,3 Jianguo Cao3

1Department of Pharmacy, Xiangya Hospital of Central South University, Changsha, 410008, People’s Republic of China; 2Department of Pharmacy, Hunan Food and Drug Vocational College, Changsha, 410208, People’s Republic of China; 3Department of Pharmaceutical Science, Medical College, Hunan Normal University, Changsha 410013, People’s Republic of China

Background: Chrysin is a natural flavonoid which has been identified as a candidate anti-cancer agent due to its inhibitory effect on a variety of cancer cells, including targeted inhibition of sphere formation in hepatocellular carcinoma (HCC) cell lines. However, the mechanism by which chrysin modulates HCC spheres remains unclear.
Materials and methods: In this study, we investigate the effect of chrysin on the regulation of SHP-1 and its downstream signal molecule STAT3 to explain the mechanism by which chrysin inhibits sphere formation of HCC cell lines.
Results: Here, we found that SHP-1 protein expression was markedly down-regulated in the spheres from both SMMC-7721 and MHCC97H cells. Chrysin significantly inhibited sphere formation and upregulated the expression of SHP-1 protein in both SMMC-7721 and MHCC97H cells, as well as reduced p-STAT3 and Twist1 expressions in SMMC-7721 cells. Furthermore, knockdown of SHP-1 in SMMC-7721 cells resulted in the induction of p-STAT3 and Twist1 protein expression and antagonizing the inhibitory effect of chrysin on sphere formation in SMMC-7721 cells.
Conclusion: Overall, the study findings demonstrated that chrysin acts as a candidate for the treatment of HCC through modulating SHP-1/STAT3 signaling pathway.

Keywords: chrysin, hepatocellular carcinoma, SHP-1, STAT3, sphere formation


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