Shih Kuang-Chung, Chan Hui-Wen, Wu Chun-Yi, Chuang Hui-Yen
Division of Endocrinology and Metabolism, Department of Medicine, Cheng-Hsin General Hospital, Taipei 11220, Taiwan.
Division of Endocrinology & Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan.
Pharmaceutics. 2023 May 17;15(5):1519. doi: 10.3390/pharmaceutics15051519.
Radiotherapy (RT) is an effective cancer treatment. The abscopal effect, referring to the unexpected shrinkage observed in non-irradiated tumors after radiation therapy, is thought to be mediated by systemic immune activation. However, it has low incidence and is unpredictable. Here, RT was combined with curcumin to investigate how curcumin affects RT-induced abscopal effects in mice with bilateral CT26 colorectal tumors. Indium 111-labeled DOTA-anti-OX40 mAb was synthesized to detect the activated T cell accumulations in primary and secondary tumors correlating with the changes in protein expressions and tumor growth to understand the overall effects of the combination of RT and curcumin. The combination treatment caused the most significant tumor suppression in both primary and secondary tumors, accompanied by the highest In-DOTA-OX40 mAb tumor accumulations. The combination treatment elevated expressions of proapoptotic proteins (Bax and cleaved caspase-3) and proinflammatory proteins (granzyme B, IL-6, and IL-1β) in both primary and secondary tumors. Based on the biodistribution of In-DOTA-OX40 mAb, tumor growth inhibition, and anti-tumor protein expression, our findings suggest that curcumin could act as an immune booster to augment RT-induced anti-tumor and abscopal effects effectively.
放射疗法(RT)是一种有效的癌症治疗方法。远隔效应是指放射治疗后在未受照射的肿瘤中观察到的意外缩小,被认为是由全身免疫激活介导的。然而,其发生率较低且不可预测。在此,将放射疗法与姜黄素相结合,以研究姜黄素如何影响双侧CT26结肠直肠癌小鼠中放射疗法诱导的远隔效应。合成了铟111标记的DOTA-抗OX40单克隆抗体,以检测原发肿瘤和继发肿瘤中活化T细胞的积累,这与蛋白质表达和肿瘤生长的变化相关,从而了解放射疗法与姜黄素联合使用的总体效果。联合治疗在原发肿瘤和继发肿瘤中均引起了最显著的肿瘤抑制,同时伴随着最高的铟-DOTA-OX40单克隆抗体肿瘤积累。联合治疗提高了原发肿瘤和继发肿瘤中促凋亡蛋白(Bax和裂解的半胱天冬酶-3)和促炎蛋白(颗粒酶B、IL-6和IL-1β)的表达。基于铟-DOTA-OX40单克隆抗体的生物分布、肿瘤生长抑制和抗肿瘤蛋白表达,我们的研究结果表明姜黄素可以作为一种免疫增强剂,有效地增强放射疗法诱导的抗肿瘤和远隔效应。