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Background <p>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 <i>Lactobacillus</i> and Simvastatin.</p> Methods <p>We utilized a cecal tumor xenograft mouse model with Ldlr<sup>−/−</sup> 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 <i>Lactobacillus</i> supplementation and Simvastatin treatment.</p> Results <p>Ldlr<sup>−/−</sup> mice on a high-cholesterol diet developed significantly larger tumors (<i>P</i> &lt; 0.05) and exhibited exacerbated malignancy, as indicated by HE and Ki-67 staining. <i>Lactobacillus</i> supplementation reduced tumor growth (<i>P</i> &lt; 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.</p> Conclusion <p>Elevated serum cholesterol promotes CRC progression, while gut microbiota remodeling through <i>Lactobacillus</i> 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月1日

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  • Xiaoliang Xie,
  • Wenjing Wang,
  • Haiming Zhang,
  • Shaohui Zhao,
  • Na Zhang,
  • Ying Gao,
  • Quanxia Liu,
  • Xiaomei Chen

摘要

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.