Astragalus polysaccharide exerts anti-tumor effects associated with altered TIGIT-CD155 axis expression in Lewis lung carcinoma models
Year: 2026
Type: article
Abstract: Background: Lung cancer remains a leading cause of cancer-related mortality worldwide. Traditional Chinese medicine (TCM), particularly the use of Astragalus membranaceus (Huangqi), has received increasing attention in the treatment of cancer. Astragalus polysaccharide (APS), the principal bioactive component of Astragalus membranaceus, has demonstrated notable antitumor and immunomodulatory effects. The T cell immunoglobulin and ITIM domain (TIGIT)-CD155 (poliovirus receptor) immune checkpoint axis has emerged as a promising therapeutic target in cancer immunotherapy. This study aimed to explore the antitumor effects of APS and elucidate its underlying mechanisms of action, including its role in the TIGIT-CD155 immune checkpoint axis in lung cancer.Methods: Lewis lung carcinoma (LLC) cells were treated with different concentrations of APS (200, 400, and 800 µg/mL). Cell viability, apoptosis, migration, and invasion were assessed using Cell Counting Kit-8 (CCK-8) assays, flow cytometry, wound healing assays, and transwell assays. Additionally, Western blot analysis was performed to evaluate the protein expression levels of TIGIT, CD155, matrix metalloproteinase-9 (MMP-9), focal adhesion kinase (FAK), Bcl-2, and BAX. In vivo experiments were conducted using an LLC mouse model, which was treated with APS and/or the TIGIT inhibitor ociperlimab. Tumor growth, immune cell infiltration, and TIGIT-CD155 expression were subsequently analyzed.Results: APS significantly inhibited LLC cell proliferation in a dose-dependent manner, with notable effects observed at concentrations ≥200 μg/mL (P<0.05). APS also promoted apoptosis by downregulating Bcl-2 and upregulating BAX expression. Additionally, APS suppressed cell migration and invasion through the downregulation of MMP-9 and FAK proteins. Notably, APS significantly reduced TIGIT and CD155 protein expression in LLC cells (P<0.05). In an LLC mouse model, APS significantly inhibited tumor growth (P<0.05), and combination treatment with Aps and a TIGIT inhibitor exerted greater antitumor effects compared with either monotherapy alone (P<0.001). APS also increased CD4+T cell infiltration and the CD4/CD8 ratio in the tumor microenvironment while reducing TIGIT and CD155 expression. Further, APS decreased the proportion of TIGIT + CD4 + T cells and TIGIT + regulatory T (Treg) cells in peripheral blood.Conclusions: APS exerts significant antitumor effects against lung cancer through multiple mechanisms, including inhibition of cell proliferation, migration, and invasion, as well as induction of apoptosis. Notably, APS modulates the tumor immune microenvironment by regulating the TIGIT-CD155 immune checkpoint axis. These experimental findings support the integration of TCM with modern immunotherapy for lung cancer treatment and provide insights into the scientific basis of the “Peiyuan Guben” (tonifying the source and consolidating the foundation) therapeutic approach in TCM oncology.
Source: Translational Cancer Research
Authors: Bing Wang, Ping Wang, Zuowei Hu
Institutions: Wuhan No.1 Hospital, Hubei University of Chinese Medicine
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7224098821