Journal article
Caerin 1.1 and 1.9 inhibit glioblastoma growth associated with modulation of the ARHGAP26-β-catenin axis and enhancing intratumoral CD8+ T cell infiltration
PLoS One, Vol.21(7), pp.1-20
2026
PMCID: PMC13349103
PMID: 42424325
Abstract
Glioblastoma (GBM) is an aggressive brain tumor with limited effective treatment options and poor patient outcomes. This study investigates the antitumor activity and underlying mechanisms of of host defense peptides caerin 1.1 (F1) and caerin 1.9 (F3) in glioblastoma models. F1/F3 treatment inhibited the proliferation of U87 cells and was associated with increased expression of ARHGAP26, suppression of β-catenin signaling pathway, and reduced the expression of downstream targets including MMP2, MMP7, and VEGFA. Cell death is primarily induced through apoptosis-related pathways, while pyroptosis-related and PI3K-related signaling showed more limited alterations. Notably, in immunodeficient NSG mice, F1/F3 altered the tumor immune microenvironment by promoting macrophage infiltration and M1-like polarization but did not significantly inhibit tumor growth. In contrast, in PBMC-humanized NSG mice, F1/F3 significantly suppressed U87 tumor growth and was associated with increased infiltration of macrophages and CD8+ T cells, together with reduced PD-L1 expression. These findings demonstrate that F1/F3 exerts both direct anti-tumor effects and immune-modulatory activities in glioblastoma models. The results support further investigation of caerin peptides as potential immunomodulatory therapeutics for glioblastoma.
Details
- Title
- Caerin 1.1 and 1.9 inhibit glioblastoma growth associated with modulation of the ARHGAP26-β-catenin axis and enhancing intratumoral CD8+ T cell infiltration
- Authors
- Furong Zhong - First Affiliated Hospital of Guangdong Pharmaceutical UniversityJinyi Wu - First Affiliated Hospital of Guangdong Pharmaceutical UniversityHongyin Wu - First Affiliated Hospital of Guangdong Pharmaceutical UniversityYichen Wang - First Affiliated Hospital of Guangdong Pharmaceutical UniversityFengyun Xiao - First Affiliated Hospital of Guangdong Pharmaceutical UniversityBin Xu - First Affiliated Hospital of Guangdong Pharmaceutical UniversityJunjie Li - Zhongao Biomedical Technology (China)Yuandong Luo - Zhongao Biomedical Technology (China)Quanlan Fu - Zhongao Biomedical Technology (China)Xiaosong Liu - First People's Hospital of FoshanTianfang Wang (Corresponding Author) - University of the Sunshine CoastGuoying Ni (Corresponding Author) - First People's Hospital of FoshanWei Zhang (Corresponding Author) - Guangdong Pharmaceutical University
- Publication details
- PLoS One, Vol.21(7), pp.1-20
- Publisher
- Public Library of Science
- Date published
- 2026
- DOI
- 10.1371/journal.pone.0353182
- ISSN
- 1932-6203
- PMID
- 42424325; PMC13349103
- Copyright note
- © 2026 Zhong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- Data Availability
- All relevant data are within the manuscript and its Supporting Information files.
- Grant note
- Zhongao Biomedical Technology (Guangdong) Co., Ltd provided support in the form of salaries for authors [JL, YL, QF, XL, GN], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
- Organisation Unit
- School of Science, Technology and Engineering
- Language
- English
- Record Identifier
- 991246197402621
- Output Type
- Journal article
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