β-hydroxybutyrate, a ketone body, suppresses tumor growth, stemness, and invasive phenotypes in non-small cell lung cancer
Lung cancer is the most common cancer worldwide. The stemness and metastasis of tumor cells present major challenges to effective lung cancer treatment. Beta-hydroxybutyrate (BHB), a ketone body, plays a key role in various cancers. However, whether BHB mediates the progression of non-small cell lun...
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| Format: | Article |
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Taylor & Francis Group
2025-12-01
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| Series: | Cancer Biology & Therapy |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/15384047.2025.2516825 |
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| author | Yunlong Huang Jiaxuan Ding Yufeng Zhu Jin Shi Rong Liu Chunmei Wu Liangfu Han Mingfeng Zhang |
| author_facet | Yunlong Huang Jiaxuan Ding Yufeng Zhu Jin Shi Rong Liu Chunmei Wu Liangfu Han Mingfeng Zhang |
| author_sort | Yunlong Huang |
| collection | DOAJ |
| description | Lung cancer is the most common cancer worldwide. The stemness and metastasis of tumor cells present major challenges to effective lung cancer treatment. Beta-hydroxybutyrate (BHB), a ketone body, plays a key role in various cancers. However, whether BHB mediates the progression of non-small cell lung cancer (NSCLC) remains unclear. The effects of BHB on the proliferation, apoptosis, and metastasis of NSCLC cells were assessed using the Cell Counting Kit 8, flow cytometry, western blotting, and Transwell assays. The sphere formation assay was used to evaluate the impact of BHB on NSCLC cell stemness. The underlying molecular mechanism was investigated through knockdown and overexpression of free fatty acid receptor 3 (FFAR3) using shRNAs and expression vectors in two NSCLC cell lines (NCI-H1975 and PC-9). In vivo, xenograft tumor and liver metastasis models were established in nude mice. BHB treatment reduced viability, stemness, and migratory and invasive abilities of NSCLC cells. BHB also induced apoptosis and increased cleaved caspase-3 levels in these cells. Moreover, BHB suppressed tumor growth and metastasis, and reduced cell stemness in NSCLC tissues in vivo. Mechanistically, FFAR3 knockdown abolished, while FFAR3 overexpression enhanced, the tumor-suppressive effects of BHB, identifying FFAR3 as a key mediator. These data shed light on the role of BHB in NSCLC development and its underlying molecular mechanisms, suggesting a promising treatment strategy for patients with NSCLC. |
| format | Article |
| id | doaj-art-06bb090096a346f3bf4cb3bbf00e99d3 |
| institution | DOAJ |
| issn | 1538-4047 1555-8576 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Cancer Biology & Therapy |
| spelling | doaj-art-06bb090096a346f3bf4cb3bbf00e99d32025-08-20T03:22:39ZengTaylor & Francis GroupCancer Biology & Therapy1538-40471555-85762025-12-0126110.1080/15384047.2025.2516825β-hydroxybutyrate, a ketone body, suppresses tumor growth, stemness, and invasive phenotypes in non-small cell lung cancerYunlong Huang0Jiaxuan Ding1Yufeng Zhu2Jin Shi3Rong Liu4Chunmei Wu5Liangfu Han6Mingfeng Zhang7Department of Oncology, Foshan Fosun Chancheng Hospital, Foshan, ChinaDepartment of Radiation Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaNanfang Hospital, Southern Medical University, Guangzhou, ChinaNanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Oncology, Foshan Fosun Chancheng Hospital, Foshan, ChinaDepartment of Oncology, Foshan Fosun Chancheng Hospital, Foshan, ChinaDepartment of Oncology, Foshan Fosun Chancheng Hospital, Foshan, ChinaDepartment of Oncology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, ChinaLung cancer is the most common cancer worldwide. The stemness and metastasis of tumor cells present major challenges to effective lung cancer treatment. Beta-hydroxybutyrate (BHB), a ketone body, plays a key role in various cancers. However, whether BHB mediates the progression of non-small cell lung cancer (NSCLC) remains unclear. The effects of BHB on the proliferation, apoptosis, and metastasis of NSCLC cells were assessed using the Cell Counting Kit 8, flow cytometry, western blotting, and Transwell assays. The sphere formation assay was used to evaluate the impact of BHB on NSCLC cell stemness. The underlying molecular mechanism was investigated through knockdown and overexpression of free fatty acid receptor 3 (FFAR3) using shRNAs and expression vectors in two NSCLC cell lines (NCI-H1975 and PC-9). In vivo, xenograft tumor and liver metastasis models were established in nude mice. BHB treatment reduced viability, stemness, and migratory and invasive abilities of NSCLC cells. BHB also induced apoptosis and increased cleaved caspase-3 levels in these cells. Moreover, BHB suppressed tumor growth and metastasis, and reduced cell stemness in NSCLC tissues in vivo. Mechanistically, FFAR3 knockdown abolished, while FFAR3 overexpression enhanced, the tumor-suppressive effects of BHB, identifying FFAR3 as a key mediator. These data shed light on the role of BHB in NSCLC development and its underlying molecular mechanisms, suggesting a promising treatment strategy for patients with NSCLC.https://www.tandfonline.com/doi/10.1080/15384047.2025.2516825Beta-hydroxybutyratenon-small cell lung cancerstemnessmetastasisFFAR3 |
| spellingShingle | Yunlong Huang Jiaxuan Ding Yufeng Zhu Jin Shi Rong Liu Chunmei Wu Liangfu Han Mingfeng Zhang β-hydroxybutyrate, a ketone body, suppresses tumor growth, stemness, and invasive phenotypes in non-small cell lung cancer Cancer Biology & Therapy Beta-hydroxybutyrate non-small cell lung cancer stemness metastasis FFAR3 |
| title | β-hydroxybutyrate, a ketone body, suppresses tumor growth, stemness, and invasive phenotypes in non-small cell lung cancer |
| title_full | β-hydroxybutyrate, a ketone body, suppresses tumor growth, stemness, and invasive phenotypes in non-small cell lung cancer |
| title_fullStr | β-hydroxybutyrate, a ketone body, suppresses tumor growth, stemness, and invasive phenotypes in non-small cell lung cancer |
| title_full_unstemmed | β-hydroxybutyrate, a ketone body, suppresses tumor growth, stemness, and invasive phenotypes in non-small cell lung cancer |
| title_short | β-hydroxybutyrate, a ketone body, suppresses tumor growth, stemness, and invasive phenotypes in non-small cell lung cancer |
| title_sort | β hydroxybutyrate a ketone body suppresses tumor growth stemness and invasive phenotypes in non small cell lung cancer |
| topic | Beta-hydroxybutyrate non-small cell lung cancer stemness metastasis FFAR3 |
| url | https://www.tandfonline.com/doi/10.1080/15384047.2025.2516825 |
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