N-acetylcysteine Remodels the Tumor Microenvironment of Primary and Recurrent Mouse Glioblastoma

Overview

Journal J Neurooncol

Publisher Springer

Date 2025 Feb 15

PMID 39954037

Authors

Xiwei Zhu

Fanen Yuan

Qian Sun

Chen Yang

Hongxiang Jiang

Xi Xiang

Xinyi Zhang

Zhiqiang Sun

Yuxin Wei

Qianxue Chen

Linzhi Cai

Affiliations

Soon will be listed here.

Abstract

Purpose: Glioblastoma (GBM) exhibits a high ROS character, giving rise to an immunosuppressive microenvironment and tumor vascular abnormality. This study investigated the potential effect of N-acetylcysteine (NAC), an antioxidant, on primary and recurrent mouse brain tumors.

Methods: We measured reactive oxygen species (ROS)/ glutathione (GSH) levels in human GBM. Additionally, we conducted NAC trials on primary mouse brain tumor models (GL261-Luc, CT2A-Luc) and a recurrent mouse GBM model (GL261-iCasp9-Luc). After brain tumor inoculation, mice received a daily 100 mg/kg NAC treatment, and the tumor volume was monitored via IVIS imaging. The efficacy of NAC was evaluated through survival time, tumor volume, ROS/GSH levels, M1/M2 macrophages, immune cells infiltration, and tumor vascularization.

Results: Human GBM suffered from significant oxidative stress. With NAC treatment, mouse brain tumors exhibited a lower ROS level, more M1-like tumor-associated macrophages/microglia (TAMs), more CD8 + T cell infiltration, and a normalized vascular character. NAC inhibited tumor growth and suppressed recurrence in mouse brain tumor models.

Conclusion: NAC is a promising adjunctive drug to remodel the brain tumors microenvironment.

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