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. 2024 Oct 2;43(22):5586–5612. doi: 10.1038/s44318-024-00257-4

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Creative Commons Public Domain Dedication waiver http://creativecommons.org/publicdomain/zero/1.0/ applies to the data associated with this article, unless otherwise stated in a credit line to the data, but does not extend to the graphical or creative elements of illustrations, charts, or figures. This waiver removes legal barriers to the re-use and mining of research data. According to standard scholarly practice, it is recommended to provide appropriate citation and attribution whenever technically possible.

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(A) MNU-induced tumor formation in GLUP-treated mice. Experimental workflow of the treatment of MNU-administrated GC mice with 1 mg/kg or 5 mg/kg GLUP via subcutaneous injection (upper, same below for GLUP treatment). In the workflow, gray arrows represent, respectively, first, second, and third cycles of MNU treatment each with a 2-week duration, and orange dashed line represents GLUP treatment with a 5-week duration. d.w., drinking water. Red circle indicated the tumor area. Macroscopic dissection view of the stomach (opened along the greater curvature) from each of MNU-induced mice with or without GLUP (lower). Red arrowhead indicated the tumor position. Scale bar, 1 cm. Data represent the representative results from two independent experiments. (B) Tumor areas of MNU-induced GC mice treated or not treated with GLUP (n = 8/group). Data are presented as means ± SD. Significance was tested using one-way ANOVA, followed by the Tukey’s post-hoc test. *p < 0.05, **p < 0.01. (C) Dual immunofluorescence staining for Ki67 and β-catenin (β-cat) in the gastric mucosa of MNU-induced GC tumors in control mice and those treated with GLUP. Scale bar, 10 μm. Data represent the representative results from two independent experiments. (D) Xenograft tumor formation assay to assess the therapeutic efficacy of 1 mg/kg or 5 mg/kg GLUP treatment (n = 5/group). A schematic illustration of the experimental workflow for a subcutaneous tumor mouse model is shown (upper). GFP-expressing HGC-27 cells were subcutaneously injected into nude mice and allowed to grow for 5 days before the resulting tumors were treated with GLUP. Representative photographs of GLUP-treated tumors are also shown (lower). Scale bar, 1 cm. Data represent the representative results from two independent experiments. (E) Measured volumes of tumors in (D) (n = 5/group). Data are presented as means ± SD. Significance was tested using one-way ANOVA, followed by the Tukey’s post-hoc test. **p < 0.01, ***p < 0.001. (F) Immunofluorescence of β-catenin and TEAD4 in tumor tissues of mice treated or not treated with GLUP. Scale bar, 10 μm. (G) RNA-scope of CTGF in the tumor tissues of mice treated or not treated with GLUP. Scale bar, 10 μm. See also Appendix Fig. S7. Source data are available online for this figure.