ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1492305
Low-dose statins restore innate immune response in breast cancer cells via suppression of mutant p53
Provisionally accepted
Zi WangMeina ShiBeijia LiuXuening Zhang
Wanjun LinYanchao Yang
Zifeng HuangDongfan YangTong ChuDayuan Zheng
Wenzhe Ma*- Macau University of Science and Technology, Taipa, Macao, SAR China
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Background: Breast cancer's high recurrence and treatment side effects demand safer, more effective therapies. Mutations in the critical TP53 gene, which normally prevents cancer, can instead promote it. This study explores if low-dose statins can curb mutant p53 activation in breast cancer's immune signaling, hindering tumor immune evasion.The study used diverse breast cancer cell lines with varying p53 statuses.Techniques included Western blot, transfection, qRT-PCR, co-immunoprecipitation, nuclear fractionation, and immunohistochemistry. In vivo experiments used BALB/c mice, with bioinformatics analysis via cBioPortal.The study found that suppressing mutant p53 restores innate immunity and enhances cancer treatment. Low-dose statins promoted IRF3 nuclear translocation by inhibiting mutant p53. Lovastatin treatment in vivo increased phosphorylated TBK1 and IRF3 levels and induced CD8+ T lymphocyte infiltration in tumors.The findings suggest low-dose statins can enhance innate immunity in breast cancer by degrading mutant p53, offering new treatment possibilities. Caution
Keywords: p53, statin, breast cancer, CGAS, STING
Received: 06 Sep 2024; Accepted: 23 Apr 2025.
Copyright: © 2025 Wang, Shi, Liu, Zhang, Lin, Yang, Huang, Yang, Chu, Zheng and Ma. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Wenzhe Ma, Macau University of Science and Technology, Taipa, Macao, SAR China
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