APR-246 combined with irradiation can enhance anti-tumor immune response against mouse 4T1 breast cancer cells
10.3760/cma.j.cn112271-20240918-00358
- VernacularTitle:APR-246联合照射增强小鼠乳腺癌4T1细胞抗肿瘤免疫应答
- Author:
Feifei MA
1
;
Tuo LI
;
Shujuan LU
;
Jianguo LI
;
Ning WANG
;
Huanteng ZHANG
;
Jiebing GUAN
;
Qiang LIU
Author Information
1. 山东第二医科大学基础医学院，潍坊 261000
- Publication Type:Journal Article
- Keywords:
Breast Cancer;
γ-rays;
APR-246;
Reactive oxygen species;
Antitumor immunity
- From:
Chinese Journal of Radiological Medicine and Protection
2025;45(4):275-281
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the effects of combining APR-246 with irradiation for enhancing anti-tumor immune response against 4T1 breast cancer cells, and to develop multiple tumor treatment strategies.Methods:The control group, APR-246 group, irradiation group and irradiation combined APR-246 group were used both in the cell experiment and tumor-bearing mice experiment. The inhibitory effect of APR-246 on the proliferation of 4T1 cells was assessed by using Cell Counting Kit-8. The effect of APR-246 with irradiation on the survival rate of 4T1 cells using clone formation assay was measured. The levels of reactive oxygen species (ROS) and lipid peroxidation (LPO) in tumor cells using a 2’, 7’-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe and a lipid peroxidation sensor, the tumor inhibition rates of different groups of tumor bearing mice were compared, and the proportions of CD4+ and CD8+ T cells and the ratio of M1/M2 macrophages were determined in the tumor microenvironment by flow cytometry.Results:Compared with irradiation group, 2, 4, 6 Gy irradiation combined APR-246 group significantly reduced the survival rates of 4T1 cells ( t = 2.89, 4.15, 2.62, P < 0.05), the 6 Gy irradiation combined APR-246 group significantly increased the levels of ROS ( t = 16.95, P < 0.05) and LPO ( t = 6.09, P < 0.05) in 4T1 cells, and significantly increased the apoptosis rate of 4T1 cells ( t = 10.99, P < 0.05). Meanwhile, from the 16 th day of tumor inoculation, the 10 Gy irradiation combined APR-246 group showed significantly inhibited tumor growth ( t = 2.38-2.91, P < 0.05) and significantly increased proportions of CD4+ and CD8+ T cells ( t = 9.96, 6.28, P < 0.05) and M1/M2 ratio ( t = 15.30, P < 0.05) in tumor tissues. Conclusions:APR-246 combined with irradiation can effectively increase ROS and LPO levels in 4T1 cells, promote tumor cell apoptosis, and induce anti-tumor immune response, thus potentially inhibiting the growth of 4T1 cells.
