Oral 25-Hydroxycholesterol Suppresses 4T1 Tumour Growth in an Immune-Context-Associated Manner
- 1Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China
- 2School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
- 3The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210029, China
Abstract
Triple-negative breast cancer (TNBC) is an aggressive subtype with limited targeted-treatment options. 25-Hydroxycholesterol (25-HC) is an oxysterol involved in metabolic and immune regulation, but its antitumour effects remain context dependent. We examined whether oral 25-HC suppresses 4T1 tumour growth in immunocompetent BALB/c mice and whether host immune status modifies the response. Mice bearing 4T1 tumours received oral vehicle or 25-HC (1 or 10 mg/kg) daily for 14 days (n = 6 per group). 25-HC reduced endpoint tumour volume from 1510.6 ± 235.4 mm3 (vehicle) to 1147.2 ± 243.1 and 866.7 ± 206.6 mm3 (adjusted p = 0.027 and 0.0004); the 10 mg/kg dose also reduced tumour weight and Ki-67 positivity, increased CD8-positive T-cell infiltration and the granzyme B (GZMB)-positive fraction, reduced M2-like macrophages and raised the M1/M2 ratio. Tumour-tissue adenosine monophosphate-activated protein kinase (AMPK) signalling was altered, with p-AMPK/AMPK increased to 1.23- and 1.57-fold of control and p-STAT6/STAT6 decreased to 0.81- and 0.46-fold. Serum 25-HC increased with dose, while intratumoral 25-HC was lowest at 10 mg/kg; no dose-associated reduction was observed in BALB/c nude mice. Oral 25-HC thus suppressed 4T1 tumour growth with immune-context-associated features; however, the treatment-by-host interaction did not reach statistical significance (p = 0.06), and immune-context association of the response remains suggestive rather than established. The reciprocal serum–tumour pattern, a descriptive observation from a single time point whose cause remains unclear, generates a testable hypothesis of immune-cell-associated 25-HC handling.
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BibTeX
@article{liang2026oral,
title = {{Oral 25-Hydroxycholesterol Suppresses 4T1 Tumour Growth in an Immune-Context-Associated Manner}},
author = {Shuo Liang and Jingyao Xu and Zining Wang and Yuhao Liu and Yanlei Xu and Chang Yao and Zhiyuan Zhu},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219735},
url = {https://www.mdpi.com/1422-0067/27/21/9735},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Oral 25-Hydroxycholesterol Suppresses 4T1 Tumour Growth in an Immune-Context-Associated Manner
AU - Shuo Liang
AU - Jingyao Xu
AU - Zining Wang
AU - Yuhao Liu
AU - Yanlei Xu
AU - Chang Yao
AU - Zhiyuan Zhu
PY - 2026
DA - 2026/10/30
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219735
UR - https://www.mdpi.com/1422-0067/27/21/9735
AB - Triple-negative breast cancer (TNBC) is an aggressive subtype with limited targeted-treatment options. 25-Hydroxycholesterol (25-HC) is an oxysterol involved in metabolic and immune regulation, but its antitumour effects remain context dependent. We examined whether oral 25-HC suppresses 4T1 tumour growth in immunocompetent BALB/c mice and whether host immune status modifies the response. Mice bearing 4T1 tumours received oral vehicle or 25-HC (1 or 10 mg/kg) daily for 14 days (n = 6 per group). 25-HC reduced endpoint tumour volume from 1510.6 ± 235.4 mm3 (vehicle) to 1147.2 ± 243.1 and 866.7 ± 206.6 mm3 (adjusted p = 0.027 and 0.0004); the 10 mg/kg dose also reduced tumour weight and Ki-67 positivity, increased CD8-positive T-cell infiltration and the granzyme B (GZMB)-positive fraction, reduced M2-like macrophages and raised the M1/M2 ratio. Tumour-tissue adenosine monophosphate-activated protein kinase (AMPK) signalling was altered, with p-AMPK/AMPK increased to 1.23- and 1.57-fold of control and p-STAT6/STAT6 decreased to 0.81- and 0.46-fold. Serum 25-HC increased with dose, while intratumoral 25-HC was lowest at 10 mg/kg; no dose-associated reduction was observed in BALB/c nude mice. Oral 25-HC thus suppressed 4T1 tumour growth with immune-context-associated features; however, the treatment-by-host interaction did not reach statistical significance (p = 0.06), and immune-context association of the response remains suggestive rather than established. The reciprocal serum–tumour pattern, a descriptive observation from a single time point whose cause remains unclear, generates a testable hypothesis of immune-cell-associated 25-HC handling.
SN - 1422-0067
ER -