Radiosensitizing effects of gut symbiotic Akkermansia muciniphila-produced propionic acid in colorectal cancer
10.3760/cma.j.cn112271-20250203-00039
- VernacularTitle:肠道共生嗜黏蛋白阿克曼氏菌代谢产物丙酸对结直肠癌放射敏感性的影响
- Author:
Yunong XIAO
1
;
Jiali DONG
1
;
Qi WANG
1
;
Yuan LI
1
;
Yanxi DONG
1
;
Jiwei QIU
1
;
Ming CUI
1
Author Information
1. 中国医学科学院北京协和医学院放射医学研究所 先进医用材料与器件国家重点实验室 天津市放射医学与分子核医学重点实验室 天津市健康研究院，天津 300192
- Publication Type:Journal Article
- Keywords:
Colorectal cancer;
Radiosensitivity;
Akkermansia muciniphila;
Propanoic acid
- From:
Chinese Journal of Radiological Medicine and Protection
2025;45(9):851-857
- CountryChina
- Language:Chinese
-
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 G 2/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 G 2/M phase block and apoptosis in colorectal cancer cells.
