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Rhein inhibits malignant phenotypes of human renal cell carcinoma by impacting on MAPK/NF-κB signaling pathways

Authors Ma YL, Chen F, Shi J

Received 11 October 2017

Accepted for publication 17 January 2018

Published 14 March 2018 Volume 2018:11 Pages 1385—1394

DOI https://doi.org/10.2147/OTT.S153798

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 2

Editor who approved publication: Dr William Cho


Ya-Li Ma,* Fang Chen,* Jun Shi

Department of Nephrology, Huaihe Hospital Henan University, Kaifeng, People’s Republic of China

*These authors contributed equally to this work

Background: Rhein, an anthraquinone derivative of rhubarb, is traditionally used in Chinese herbal medicine. Now emerging studies suggest its antitumor properties in many human cancers. The present study aims to investigate the antitumor role of Rhein and its possible mechanism in human renal cell carcinoma (RCC).
Materials and methods: Three RCC cell lines (A489, 786-O and ACHN) were used as the cell models. We applied CCK-8, cell counting, colony formation, wound healing and Transwell assays to assess the antitumor roles of Rhein in RCC cells in vitro. The therapeutic efficacy of Rhein was further evaluated by intraperitoneal administrations in tumor formation of mice. Western blot was used to investigate the underlying mechanisms of action of Rhein.
Results: Rhein inhibited RCC cell proliferation in a dose- and time-dependent manner. It also suppressed RCC cell migration and invasion in vitro. Moreover, Rhein was able to inhibit tumor growth in nude mice by intraperitoneal administration in vivo. Mechanistically, the protein levels of phosphorylated MAPK (mitogen-activated protein kinase, extracellular signal-regulated kinase and c-Jun N-terminal kinase), phosphorylated Akt and two targets of NF-κB (nuclear factor kappa-light-chain enhancer of activated B cells) pathway, matrix metalloproteinase 9 and CCND1 were all markedly reduced by Rhein treatment.
Conclusion: Rhein processed the antitumor effects in RCC cells by inhibiting cell proliferation, migration and invasion, and these tumor-suppressing functions might be mediated by MAPK/NF-κB signaling pathways.

Keywords: Rhein, renal cell carcinoma, antitumor effects, MAPK, NF-κB

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