| 马菲菲,李拓,陆淑娟,等.APR-246联合照射增强小鼠乳腺癌4T1细胞抗肿瘤免疫应答[J].中华放射医学与防护杂志,2025,45(4):275-281.Ma Feifei,Li Tuo,Lu Shujuan,et al.APR-246 combined with irradiation can enhance anti-tumor immune response against mouse 4T1 breast cancer cells[J].Chin J Radiol Med Prot,2025,45(4):275-281 |
| APR-246联合照射增强小鼠乳腺癌4T1细胞抗肿瘤免疫应答 |
| APR-246 combined with irradiation can enhance anti-tumor immune response against mouse 4T1 breast cancer cells |
| 投稿时间：2024-09-18 |
| DOI：10.3760/cma.j.cn112271-20240918-00358 |
| 中文关键词: 乳腺癌 γ射线 APR-246 活性氧 抗肿瘤免疫 |
| 英文关键词:Breast Cancer γ-rays APR-246 Reactive oxygen species Antitumor immunity |
| 基金项目:国家自然科学基金(32071241);辐射防护实验室开放基金(CIRP-DTRI20220202) |
| 作者 | 单位 | E-mail | | 马菲菲 | 山东第二医科大学基础医学院, 潍坊 261000
中国医学科学院放射医学研究所天津市放射医学与分子核医学重点实验室, 天津 300192
山东枣庄市山亭区人民医院放射科, 枣庄 277200 | | | 李拓 | 山东第二医科大学基础医学院, 潍坊 261000
中国医学科学院放射医学研究所天津市放射医学与分子核医学重点实验室, 天津 300192 | | | 陆淑娟 | 山东枣庄市山亭区人民医院放射科, 枣庄 277200 | | | 李建国 | 山东第二医科大学基础医学院, 潍坊 261000 | | | 王宁 | 山东第二医科大学基础医学院, 潍坊 261000
中国医学科学院放射医学研究所天津市放射医学与分子核医学重点实验室, 天津 300192 | | | 张焕腾 | 中国医学科学院放射医学研究所天津市放射医学与分子核医学重点实验室, 天津 300192 | | | 管杰冰 | 山东第二医科大学基础医学院, 潍坊 261000
中国医学科学院放射医学研究所天津市放射医学与分子核医学重点实验室, 天津 300192 | | | 刘强 | 山东第二医科大学基础医学院, 潍坊 261000
中国医学科学院放射医学研究所天津市放射医学与分子核医学重点实验室, 天津 300192 | liuqiang@irm-cams.ac.cn |
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| 中文摘要: |
| 目的 探究APR-246联合照射增强乳腺癌细胞4T1的抗肿瘤免疫应答,开发多重肿瘤治疗策略。方法 细胞实验及荷瘤小鼠实验均分为对照组、给药组、照射组和照射+给药组。利用CCK-8实验检测APR-246对4T1肿瘤细胞的增殖抑制,通过克隆形成实验证实APR-246联合照射对4T1细胞的存活率的影响,使用 2’,7’-二 氯二氢荧光素的氧化双乙酸酯(DCFH-DA)荧光探针以及脂质过氧化传感器检测肿瘤细胞中活性氧(ROS)及脂质过氧化(LPO)水平,比较各组荷瘤小鼠抑瘤率,通过流式细胞术检测肿瘤微环境中CD4+、CD8+T细胞比例及M1/M2型巨噬细胞的极化比例。结果 与照射组相比,比较各组荷瘤小鼠抑瘤率,2、4、6 Gy照射+给药组可有效降低4T1细胞的存活率(t =2.89、4.15、2.62,P < 0.05);6 Gy照射时,照射+给药组可升高4T1细胞内的ROS(t=16.95,P < 0.05)和LPO(t =6.09,P < 0.05),显著提高4T1细胞的凋亡比例(t=10.99,P < 0.05)。同时,照射+给药组的荷瘤小鼠的肿瘤生长受到明显抑制(t =2.38~2.91,P < 0.05),肿瘤组织中CD4+、CD8+T细胞比例(t=9.96、6.28,P < 0.05)及M1/M2型巨噬细胞比例(t=15.30,P < 0.05)显著提高。结论 APR-246联合照射可有效升高4T1细胞内的ROS水平及LPO水平,促进细胞凋亡,诱导抗肿瘤免疫反应,从而抑制4T1细胞生长。 |
| 英文摘要: |
| 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 16th 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. |
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