e over activation of Wnt pathway can induce the occurrence of main liver IL-23 Inhibitor list cancer in mice. In sufferers with liver cancer, Wnt pathway is the signal pathway with the highest mutationrate except p53 (Trejo-Solis et al., 2021). Wnt pathway inhibitors can not just FP Antagonist drug inhibit the growth of HCC cells, but additionally minimize the drug resistance of cells and sensitize chemotherapeutic drugs (Vilchez et al., 2016). -catenin protein is definitely the key transduction issue to begin Wnt pathway transcription. In the inactive Wnt pathway, the degree 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 sizable level of -catenin accumulate and transfer towards the nucleus. Therefore, excessive activation of Wnt pathway can market tumor occurrence and development. The present study found that sempervirine could substantially inhibit the nuclear aggregation amount of -catenin, indicating that sempervirine may perhaps 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 growth in vivo and increatingly, possessed a synergistic impact with sorafenib. Additionally, sempervirine could drastically inhibit the nuclear aggregation level of -catenin and inhibit the transcription degree of Wnt pathway and therefore could induce HCC apoptosis by way of the Wnt/-catenin pathway.Information AVAILABILITY STATEMENTThe original contributions presented within the study are incorporated inside the article/Supplementary Material, additional inquiries can be directed towards the corresponding authors.ETHICS STATEMENTThe animal study was reviewed and authorized by Fujian Health-related University.AUTHOR CONTRIBUTIONSPC, GJ, CY, and RY made investigation; 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 function was supported by the National Organic Science Foundation of China (82000554, 81973309), the Organic Science Foundation of Fujian Province (2019J01303, 2020J01640, 2020J01618), the Science and Technologies Project of Fujian Province (2018Y2001), the Analysis Initiation Fund for High-level Talents of Fujian Medical University (XRCZX2018015), the Startup Fund of Fujian Medical University (2018QH1015), the Joint Funds for the Innovation of Science and Technology, Fujian Province (2018Y9075, 2019Y9009) along with the Open Project Fund of Fujian Provincial Crucial Laboratory of Atmosphere Variables 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 evaluation.SUPPLEMENTARY MATERIALThe Supplementary Material for this article could be identified on the web 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:ten.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.