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Radix Tetrastigma hemsleyani flavone exhibits antitumor activity in colorectal cancer via Wnt/β-catenin signaling pathway

Authors Wu X, Yu N, Zhang Y, Ye Y, Sun W, Ye L, Wu H, Yang Z, Wu L, Wang F

Received 23 April 2018

Accepted for publication 23 June 2018

Published 4 October 2018 Volume 2018:11 Pages 6437—6446

DOI https://doi.org/10.2147/OTT.S172048

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Manfred Beleut

Peer reviewer comments 2

Editor who approved publication: Dr Samir Farghaly


Xiaowei Wu,1,* Na Yu,1,* Yuping Zhang,2 Yuanning Ye,2 Wenrong Sun,1 Lei Ye,1 Huimin Wu,3 Zhao Yang,2 Lin Wu,1 Fangyu Wang3

1Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing, China; 2Department of Gastroenterology and Hepatology, Jinling Hospital, Southern Medical University, Guangzhou, China; 3Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China

*These authors contributed equally to this work

Background:
Radix Tetrastigma hemsleyani flavone (RTHF) is extracted from a traditional Chinese medicinal herb T. hemsleyani, which is conventionally used as a folk medicine for its anti-inflammation activity and antiviral activity. In this study, the effects of RTHF on inhibiting malignant biological properties in colorectal cancer (CRC) were evaluated by conducting both in vitro and in vivo experiments, and the underlying mechanism was investigated.
Materials and methods: Cell Counting Kit-8, colony formation, and flow cytometry assays were performed to evaluate the proliferation of RTHF-treated colon tumor cells. Migration and invasion capacities were also tested by cell wound scratch assay and Transwell invasion assay. Moreover, the antitumor effects of RTHF on azoxymethane/dextran sulfate sodium-induced colitis-related CRC were investigated in C57BL/6 mice. In addition, Western blot and/or quantitative reverse transcription polymerase chain reaction analysis were used to evaluate the expressions of Lgr5, Cyclin D1, c-Myc, and E-cadherin.
Results: These experiments showed that RTHF could decrease the cell growth kinetics and clone-forming capacity. RTHF could also dose dependently induce cell cycle arrest at G0/G1 phase and inhibit epithelial -mesenchymal transition process. Furthermore, downregulation of β-catenin activation and downstream protein expression were detected in CRC cells after being treated with RTHF. RTHF daily gavage suppressed the number and size of CRC in mice and inhibited Lgr5 and Cyclin D1 expressions in tumor tissue.
Conclusion: In conclusion, RTHF treatment inhibits colorectal tumor growth, decreases Wnt/β-catenin pathway activity, and downregulates target genes’ expression.

Keywords: radix Tetrastigma hemsleyani, flavone, colorectal cancer, Wnt/β-catenin, proliferation, migration
 

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