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

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 RTFIF 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 beta-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 DI expressions in tumor tissue. Conclusion: In conclusion, RTHF treatment inhibits colorectal tumor growth, decreases Wnt/beta-catenin pathway activity, and downregulates target genes' expression.