e over activation of Wnt pathway can induce the occurrence of key liver cancer in mice. In patients with liver cancer, Wnt pathway may be the signal pathway with all the highest mutationrate except p53 (Trejo-Solis et al., 2021). Wnt pathway inhibitors can not just inhibit the development of HCC cells, but in addition cut down the drug resistance of cells and CaMK II Inhibitor Compound sensitize chemotherapeutic drugs (Vilchez et al., 2016). -catenin protein is definitely the essential transduction element to begin Wnt pathway transcription. Inside the inactive Wnt pathway, the level of -catenin is strictly regulated by GSK3 complicated, which keeps Wnt activity at a low level. In tumor cells, Wnt pathway mutation or upstream signal activation makes a big volume of -catenin accumulate and transfer for the nucleus. As a result, excessive activation of Wnt pathway can promote tumor occurrence and improvement. The present study discovered that sempervirine could significantly inhibit the nuclear aggregation level of -catenin, indicating that sempervirine may well act on the transcriptional activity of -catenin to regulate cell proliferation. In conclusion, the present study maintained that sempervirine inhibited HCC by arresting G1 cell cycle and inducing apoptosis. Additionally, sempervirine inhibited HCC development in vivo and increatingly, possessed a synergistic effect with sorafenib. Additionally, sempervirine could drastically inhibit the nuclear aggregation amount of -catenin and inhibit the transcription amount of Wnt pathway and therefore could possibly induce HCC apoptosis by way of the Wnt/-catenin pathway.Information AVAILABILITY STATEMENTThe original contributions presented inside the study are integrated inside the article/Supplementary Material, additional inquiries is often directed to the corresponding authors.ETHICS STATEMENTThe animal study was reviewed and authorized by Fujian IL-17 Inhibitor Purity & Documentation Health-related University.AUTHOR CONTRIBUTIONSPC, GJ, CY, and RY made research; RY, HL, YH, DS, YL, YL, and YS performed the experiments; RY, HL, YH and GJ analyzed data; and RY and CY wrote the manuscript.FUNDINGThis perform was supported by the National Organic Science Foundation of China (82000554, 81973309), the All-natural Science Foundation of Fujian Province (2019J01303, 2020J01640, 2020J01618), the Science and Technologies Project of Fujian Province (2018Y2001), the Study Initiation Fund for High-level Talents of Fujian Health-related University (XRCZX2018015), the Startup Fund of Fujian Health-related University (2018QH1015), the Joint Funds for the Innovation of Science and Technology, Fujian Province (2018Y9075, 2019Y9009) as well as the Open Project Fund of Fujian Provincial Important Laboratory of Atmosphere Things and Cancer (GWSZD-202003).Frontiers in Pharmacology | frontiersin.orgDecember 2021 | Volume 12 | ArticleYue et al.Sempervirine Inhibits HCC by WntACKNOWLEDGMENTSWe thank Junjin Lin in the Public Technology Service Center (Fujian Healthcare University, China) for the help in flow cytometry analysis.SUPPLEMENTARY MATERIALThe Supplementary Material for this short article might be discovered online at: frontiersin.org/articles/10.3389/fphar.2021.806091/ full#supplementary-materialMullard, A. (2016). Pioneering Apoptosis-Targeted Cancer Drug Poised for FDA Approval. Nat. Rev. Drug Discov. 15, 14749. doi:10.1038/nrd.2016.23 Pan, X., Yang, C., Cleveland, J. L., and Bannister, T. D. (2016). Synthesis and Cytoxicity of Sempervirine and Analogues. J. Org. Chem. 81, 2194200. doi:10.1021/acs.joc.6b00022 Parsons, M. J., Tammela, T., and Dow, L. E. (2021). WNT as a Driver and Dependency in Cancer. Cancer Discov.