Cholesterol-induced colorectal cancer progression and its mitigation through gut microbiota remodeling and simvastatin treatment

  • BMC Cancer. 2025 Jun 1;25(1):977. doi: 10.1186/s12885-025-14379-3.
Xiaoliang Xie  #  1 ,  Wenjing Wang  #  2 ,  Haiming Zhang  2 ,  Shaohui Zhao  2 ,  Na Zhang  3 ,  Ying Gao  4 ,  Quanxia Liu  5 ,  Xiaomei Chen  6
Affiliations
  • 1. Department of Colorectal Surgery, General Hospital of Ningxia Medical University, Yinchuan, 750004, China.
  • 2. Ningxia Medical University, Yinchuan, 750004, China.
  • 3. Department of Obstetrics and Gynecology, Ningxia Hui Autonomous Region People's Hospital, Yinchuan, 750004, China.
  • 4. Department of Oncology, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, Ningxia, China.
  • 5. The Second Department of Oncology, Ningxia Medical University General Hospital, Yinchuan, 750004, China. [email protected].
  • 6. Department of Geriatrics, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China. [email protected].
  • # Contributed equally.
PMID: 40452015 DOI: 10.1186/s12885-025-14379-3
Abstract

Background: Elevated serum Cholesterol levels are linked to an increased risk of colorectal adenomas and colorectal Cancer (CRC), yet the role of serum low-density lipoprotein (LDL) in CRC development remains unclear. This study explores the impact of Cholesterol on tumor growth and the potential therapeutic effects of Lactobacillus and Simvastatin.

Methods: We utilized a cecal tumor xenograft mouse model with LDLR-/- mice to assess the effects of high Cholesterol levels on tumor growth. Additionally, the role of gut microbiota remodeling and cholesterol-lowering strategies was investigated using Lactobacillus supplementation and Simvastatin treatment.

Results: LDLR-/- mice on a high-cholesterol diet developed significantly larger tumors (P < 0.05) and exhibited exacerbated malignancy, as indicated by HE and Ki-67 staining. Lactobacillus supplementation reduced tumor growth (P < 0.05), lowered serum Cholesterol levels, and altered the gut microbiota composition, increasing the relative abundance of beneficial Bacterial taxa. Simvastatin treatment reduced PD-L1 expression in CRC cells by lowering Cholesterol levels, which was associated with decreased CRC proliferation, reduced serum LDL levels, and enhanced T cell infiltration in the tumor microenvironment.

Conclusion: Elevated serum Cholesterol promotes CRC progression, while gut microbiota remodeling through Lactobacillus supplementation and cholesterol-lowering interventions, such as Simvastatin, show potential in mitigating tumor growth and enhancing antitumor immune responses. These findings highlight the importance of Cholesterol management in CRC treatment strategies.

Keywords
Lactobacillus; Colorectal cancer; Gut microbiota; Low-density lipoprotein; Simvastatin.
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