Radiation induced dermatitis by increasing triglyceride levels to induce autophagy and inhibit the PI3K/Akt/mTOR signaling pathway
Abstract Background Radiodermatitis (RD) is the primary acute adverse effect experienced by patients receiving radiotherapy (RT) for head and neck cancer (HNC). This study aimed to investigate the correlation between triglyceride (TG) levels and the severity of RD, as well as the underlying mechanis...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-04-01
|
| Series: | Lipids in Health and Disease |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12944-025-02553-2 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850145011992100864 |
|---|---|
| author | Yafang Hong Hongdan Guan Yunhao Chen Yao Wang Junjian Lin Ying Wang Yang Zhang Rong Zheng Xingchen Ding Zihan Zhou Benhua Xu |
| author_facet | Yafang Hong Hongdan Guan Yunhao Chen Yao Wang Junjian Lin Ying Wang Yang Zhang Rong Zheng Xingchen Ding Zihan Zhou Benhua Xu |
| author_sort | Yafang Hong |
| collection | DOAJ |
| description | Abstract Background Radiodermatitis (RD) is the primary acute adverse effect experienced by patients receiving radiotherapy (RT) for head and neck cancer (HNC). This study aimed to investigate the correlation between triglyceride (TG) levels and the severity of RD, as well as the underlying mechanisms involved. Methods Data were collected from 248 patients with locally advanced HNC treated with intensity-modulated radiation therapy (IMRT). Clinical characteristics and blood profiles prior to RT were collected. After RT, RD severity was assessed. A binary logistic regression analysis was used to determine risk factors. Mouse models of RD were established by administering radiating at a dose of 9 Gy over two consecutive days. TG levels in the mice and cells were quantified using an automatic biochemical analyzer and a TG assay kit, respectively. Cell viability was detected by the Cell Counting Kit-8 (CCK-8) assay, while apoptotic cell percentages were measured via flow cytometry. Western blotting assay was used to analyze the protein levels in the cells of interest. Results The TG level was the sole independent risk factor for grade 3 or higher (grade 3+) RD. Radiation was found to increase the TG content in both mouse blood and skin cells. Skin cells with high TG contents presented more severe radiation-induced damage when the radiation dose administered was 9 Gy over two consecutive days. The administration of 200 µmol/L palmitic acid (PA) or 2 Gy radiation independently did not affect HaCaT cell proliferation or apoptosis rates. Their combination was shown to induce skin cell injury. Mechanistically, autophagy was excessively activated. Furthermore, the protein concentrations of phospho-PI3K, phospho-Akt, and phospho-mTOR were notably decreased. Conclusions TGs are crucially involved in the development of RD. Increased TG levels after radiation treatment suppress the PI3K/Akt/mTOR pathway, induce autophagy, and exacerbate RD. |
| format | Article |
| id | doaj-art-0ddaf07f1ab2472bb51b40c75d062ac0 |
| institution | OA Journals |
| issn | 1476-511X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Lipids in Health and Disease |
| spelling | doaj-art-0ddaf07f1ab2472bb51b40c75d062ac02025-08-20T02:28:11ZengBMCLipids in Health and Disease1476-511X2025-04-0124111310.1186/s12944-025-02553-2Radiation induced dermatitis by increasing triglyceride levels to induce autophagy and inhibit the PI3K/Akt/mTOR signaling pathwayYafang Hong0Hongdan Guan1Yunhao Chen2Yao Wang3Junjian Lin4Ying Wang5Yang Zhang6Rong Zheng7Xingchen Ding8Zihan Zhou9Benhua Xu10Department of Radiation Oncology, Fujian Medical University Union HospitalDepartment of Radiation Oncology, Fujian Medical University Union HospitalDepartment of Radiation Oncology, Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer ResearchDepartment of Radiation Oncology, Fujian Medical University Union HospitalDepartment of Radiation Oncology, Fujian Medical University Union HospitalDepartment of Radiation Oncology, Fujian Medical University Union HospitalDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical SciencesDepartment of Radiation Oncology, Fujian Medical University Union HospitalDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical SciencesDepartment of Radiation Oncology, Fujian Medical University Union HospitalDepartment of Radiation Oncology, Fujian Medical University Union HospitalAbstract Background Radiodermatitis (RD) is the primary acute adverse effect experienced by patients receiving radiotherapy (RT) for head and neck cancer (HNC). This study aimed to investigate the correlation between triglyceride (TG) levels and the severity of RD, as well as the underlying mechanisms involved. Methods Data were collected from 248 patients with locally advanced HNC treated with intensity-modulated radiation therapy (IMRT). Clinical characteristics and blood profiles prior to RT were collected. After RT, RD severity was assessed. A binary logistic regression analysis was used to determine risk factors. Mouse models of RD were established by administering radiating at a dose of 9 Gy over two consecutive days. TG levels in the mice and cells were quantified using an automatic biochemical analyzer and a TG assay kit, respectively. Cell viability was detected by the Cell Counting Kit-8 (CCK-8) assay, while apoptotic cell percentages were measured via flow cytometry. Western blotting assay was used to analyze the protein levels in the cells of interest. Results The TG level was the sole independent risk factor for grade 3 or higher (grade 3+) RD. Radiation was found to increase the TG content in both mouse blood and skin cells. Skin cells with high TG contents presented more severe radiation-induced damage when the radiation dose administered was 9 Gy over two consecutive days. The administration of 200 µmol/L palmitic acid (PA) or 2 Gy radiation independently did not affect HaCaT cell proliferation or apoptosis rates. Their combination was shown to induce skin cell injury. Mechanistically, autophagy was excessively activated. Furthermore, the protein concentrations of phospho-PI3K, phospho-Akt, and phospho-mTOR were notably decreased. Conclusions TGs are crucially involved in the development of RD. Increased TG levels after radiation treatment suppress the PI3K/Akt/mTOR pathway, induce autophagy, and exacerbate RD.https://doi.org/10.1186/s12944-025-02553-2Head and neck cancerRadiodermatitisTriglycerideAutophagyPI3K/Akt/mTOR pathway |
| spellingShingle | Yafang Hong Hongdan Guan Yunhao Chen Yao Wang Junjian Lin Ying Wang Yang Zhang Rong Zheng Xingchen Ding Zihan Zhou Benhua Xu Radiation induced dermatitis by increasing triglyceride levels to induce autophagy and inhibit the PI3K/Akt/mTOR signaling pathway Lipids in Health and Disease Head and neck cancer Radiodermatitis Triglyceride Autophagy PI3K/Akt/mTOR pathway |
| title | Radiation induced dermatitis by increasing triglyceride levels to induce autophagy and inhibit the PI3K/Akt/mTOR signaling pathway |
| title_full | Radiation induced dermatitis by increasing triglyceride levels to induce autophagy and inhibit the PI3K/Akt/mTOR signaling pathway |
| title_fullStr | Radiation induced dermatitis by increasing triglyceride levels to induce autophagy and inhibit the PI3K/Akt/mTOR signaling pathway |
| title_full_unstemmed | Radiation induced dermatitis by increasing triglyceride levels to induce autophagy and inhibit the PI3K/Akt/mTOR signaling pathway |
| title_short | Radiation induced dermatitis by increasing triglyceride levels to induce autophagy and inhibit the PI3K/Akt/mTOR signaling pathway |
| title_sort | radiation induced dermatitis by increasing triglyceride levels to induce autophagy and inhibit the pi3k akt mtor signaling pathway |
| topic | Head and neck cancer Radiodermatitis Triglyceride Autophagy PI3K/Akt/mTOR pathway |
| url | https://doi.org/10.1186/s12944-025-02553-2 |
| work_keys_str_mv | AT yafanghong radiationinduceddermatitisbyincreasingtriglyceridelevelstoinduceautophagyandinhibitthepi3kaktmtorsignalingpathway AT hongdanguan radiationinduceddermatitisbyincreasingtriglyceridelevelstoinduceautophagyandinhibitthepi3kaktmtorsignalingpathway AT yunhaochen radiationinduceddermatitisbyincreasingtriglyceridelevelstoinduceautophagyandinhibitthepi3kaktmtorsignalingpathway AT yaowang radiationinduceddermatitisbyincreasingtriglyceridelevelstoinduceautophagyandinhibitthepi3kaktmtorsignalingpathway AT junjianlin radiationinduceddermatitisbyincreasingtriglyceridelevelstoinduceautophagyandinhibitthepi3kaktmtorsignalingpathway AT yingwang radiationinduceddermatitisbyincreasingtriglyceridelevelstoinduceautophagyandinhibitthepi3kaktmtorsignalingpathway AT yangzhang radiationinduceddermatitisbyincreasingtriglyceridelevelstoinduceautophagyandinhibitthepi3kaktmtorsignalingpathway AT rongzheng radiationinduceddermatitisbyincreasingtriglyceridelevelstoinduceautophagyandinhibitthepi3kaktmtorsignalingpathway AT xingchending radiationinduceddermatitisbyincreasingtriglyceridelevelstoinduceautophagyandinhibitthepi3kaktmtorsignalingpathway AT zihanzhou radiationinduceddermatitisbyincreasingtriglyceridelevelstoinduceautophagyandinhibitthepi3kaktmtorsignalingpathway AT benhuaxu radiationinduceddermatitisbyincreasingtriglyceridelevelstoinduceautophagyandinhibitthepi3kaktmtorsignalingpathway |