| Xiao Yunong,Dong Jiali,Wang Qi,et al.Radiosensitizing effects of gut symbiotic Akkermansia muciniphila-produced propionic acid in colorectal cancer[J].Chinese Journal of Radiological Medicine and Protection,2025,45(9):851-857 |
| Radiosensitizing effects of gut symbiotic Akkermansia muciniphila-produced propionic acid in colorectal cancer |
| Received:February 03, 2025 |
| DOI：10.3760/cma.j.cn112271-20250203-00039 |
| KeyWords:Colorectal cancer Radiosensitivity Akkermansia muciniphila Propanoic acid |
| FundProject:国家自然科学基金(82202944,82373524,32100087);中央高校基本科研业务费专项资金(3332024214) |
| Author Name | Affiliation | E-mail | | Xiao Yunong | State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Tianjin Institutes of Health Science, Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China | | | Dong Jiali | State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Tianjin Institutes of Health Science, Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China | | | Wang Qi | State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Tianjin Institutes of Health Science, Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China | | | Li Yuan | State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Tianjin Institutes of Health Science, Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China | | | Dong Yanxi | State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Tianjin Institutes of Health Science, Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China | | | Qiu Jiwei | State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Tianjin Institutes of Health Science, Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China | | | Cui Ming | State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Tianjin Institutes of Health Science, Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China | cuiming0403@bjmu.edu.cn |
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| Abstract:: |
| Objective To investigate the effects of propionic acid produced by Akkermansia muciniphila on the radiosensitivity of colorectal cancer and the underlying mechanism. Methods Normal human colon mucosal epithelial cells (NCM460) were used to determine the appropriate concentration of propionic acid. Human colorectal cancer cells (HCT-8) were treated with A. muciniphila-conditioned medium or propionic acid, followed by exposure to 6 Gy γ-ray irradiation, and cell survival and proliferation were measured by clone formation assay and Cell Counting Kit-8 (CCK-8) assay, respectively. A mouse model of colorectal cancer was established using azoxymethane/dextran sodium sulfate. The mice were divided into control model group, irradiation group, and irradiation+propionic acid group. Their body weight, colorectal length, tumor count, and tumor area were recorded. The radiosensitizing effect of propionic acid was assessed with HE staining, immunohistochemical staining, and enzyme-linked immunosorbent assay. The mechanism was explored by using RT-PCR and flow cytometry. Results CCK-8 assay showed that 1-mmol/L propionic acid had no significant effect on the proliferation of NCM460 cells (P > 0.05), which was used for subsequent experiments. Pretreated with A. muciniphila-conditioned medium or propionic acid, the survival and proliferation abilities of irradiated HCT cells were significantly decreased (t = 3.14-34.98, P < 0.05). Compared with the irradiation group, the colorectal cancer mice in the irradiation+propionic acid group showed a significantly longer colorectal length (t = 3.50, P < 0.05) and a significantly smaller number of tumors (t = 3.48, P < 0.05); the two groups had significantly smaller tumor areas than the control model group (t = 5.97, 7.30, P < 0.05). HE staining and immunohistochemical staining showed that propionic acid restored colorectal structure, and decreased Ki67 expression in colorectal tissue (t = 14.50, 3.40, P < 0.05). Propionic acid treatment significantly reduced the levels of the inflammatory factors interleukin-6 and tumor necrosis factor-α, as compared with the mice receiving irradiation alone (t = 4.86, 5.06, P < 0.05). Irradiation plus propionic acid treatment significantly increased p53 expression and significantly aggravated G2/M phase block and cell apoptosis (t = 20.35, 13.05, P < 0.05). Conclusions The A. muciniphila metabolite propionic acid plays a sensitizing role in radiation therapy for colorectal cancer by promoting G2/M phase block and apoptosis in colorectal cancer cells. |
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