Cholesterol-induced colorectal cancer progression and its mitigation through gut microbiota remodeling and simvastatin treatment
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 pote...
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| Language: | English |
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BMC
2025-06-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-025-14379-3 |
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| author | Xiaoliang Xie Wenjing Wang Haiming Zhang Shaohui Zhao Na Zhang Ying Gao Quanxia Liu Xiaomei Chen |
| author_facet | Xiaoliang Xie Wenjing Wang Haiming Zhang Shaohui Zhao Na Zhang Ying Gao Quanxia Liu Xiaomei Chen |
| author_sort | Xiaoliang Xie |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ebc5748e3ef042f5afd1daf9f7bf11e5 |
| institution | DOAJ |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj-art-ebc5748e3ef042f5afd1daf9f7bf11e52025-08-20T03:10:37ZengBMCBMC Cancer1471-24072025-06-0125111110.1186/s12885-025-14379-3Cholesterol-induced colorectal cancer progression and its mitigation through gut microbiota remodeling and simvastatin treatmentXiaoliang Xie0Wenjing Wang1Haiming Zhang2Shaohui Zhao3Na Zhang4Ying Gao5Quanxia Liu6Xiaomei Chen7Department of Colorectal Surgery, General Hospital of Ningxia Medical UniversityNingxia Medical UniversityNingxia Medical UniversityNingxia Medical UniversityDepartment of Obstetrics and Gynecology, Ningxia Hui Autonomous Region People’s HospitalDepartment of Oncology, People’s Hospital of Ningxia Hui Autonomous RegionThe Second Department of Oncology, Ningxia Medical University General HospitalDepartment of Geriatrics, Hospital of Chengdu University of Traditional Chinese MedicineAbstract 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.https://doi.org/10.1186/s12885-025-14379-3Colorectal cancerLow-density lipoproteinGut microbiotaSimvastatinLactobacillus |
| spellingShingle | Xiaoliang Xie Wenjing Wang Haiming Zhang Shaohui Zhao Na Zhang Ying Gao Quanxia Liu Xiaomei Chen Cholesterol-induced colorectal cancer progression and its mitigation through gut microbiota remodeling and simvastatin treatment BMC Cancer Colorectal cancer Low-density lipoprotein Gut microbiota Simvastatin Lactobacillus |
| title | Cholesterol-induced colorectal cancer progression and its mitigation through gut microbiota remodeling and simvastatin treatment |
| title_full | Cholesterol-induced colorectal cancer progression and its mitigation through gut microbiota remodeling and simvastatin treatment |
| title_fullStr | Cholesterol-induced colorectal cancer progression and its mitigation through gut microbiota remodeling and simvastatin treatment |
| title_full_unstemmed | Cholesterol-induced colorectal cancer progression and its mitigation through gut microbiota remodeling and simvastatin treatment |
| title_short | Cholesterol-induced colorectal cancer progression and its mitigation through gut microbiota remodeling and simvastatin treatment |
| title_sort | cholesterol induced colorectal cancer progression and its mitigation through gut microbiota remodeling and simvastatin treatment |
| topic | Colorectal cancer Low-density lipoprotein Gut microbiota Simvastatin Lactobacillus |
| url | https://doi.org/10.1186/s12885-025-14379-3 |
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