Qian Liping, Mao Lihua, Mo Weixing, Wang Rong, Zhang Yunlong
Radiology Department, Hangzhou Cancer Hospital, Hangzhou City, 310002 Zhejiang Province, China.
Radiology Department, Yuyao People's Hospital, Yuyao City, 315400 Zhejiang Province, China.
J Oncol. 2022 Oct 13;2022:9672773. doi: 10.1155/2022/9672773. eCollection 2022.
Glioblastoma (GBM) is the most common intracranial tumor with characteristic of malignancy. Resveratrol, a natural originated polyphenolic compound, has been reported to act as a potential radiosensitizer in cancer therapy. Magnetic resonance imaging (MRI) is the first choice for the diagnosis, pathological grading, and efficacy evaluation of GBM. In this study, MRI was applied to observe whether resveratrol could intensify the anti-GBM tumor effect by enhancing antitumor immunity during radiotherapy. We established an intracranial C6 GBM model in SD rats, treated with radiation and resveratrol. The increased body weight, the inhibition on mortality, and tumor volume in radiated- GBM rats were further enhanced by resveratrol addition, while the pathological damage of brain was alleviated. The modulation of radiation on inflammation, cell cycle, and apoptosis was strengthened by resveratrol; and Ki-67, PD-L1, and cell cycle- and apoptosis-related protein expressions were also improved by cotreatment. Besides, cotreatment attenuated DNA damage and induced G0/G1-phase cell arrest of GBM rats, accompanied with the changed expression of ATM-AKT-STAT3 pathway-related proteins. Moreover, the percentages of CD3CD8T cells and IFN- CD8T cells were enhanced, while (CD4CD25Foxp3)/CD4T cells were decreased by radiation or resveratrol, which was strengthened by cotreatment. The modulation effect of cotreatment on CD3, Foxp3, and IFN- levels was also stronger than radiation or resveratrol alone. To conclude, resveratrol enhanced the effect of radiotherapy by inducing DNA damage and antitumor immunity in the intracranial C6 GBM.
胶质母细胞瘤（GBM）是最常见的具有恶性特征的颅内肿瘤。白藜芦醇是一种天然来源的多酚类化合物，据报道在癌症治疗中可作为一种潜在的放射增敏剂。磁共振成像（MRI）是GBM诊断、病理分级及疗效评估的首选方法。在本研究中，应用MRI观察白藜芦醇在放疗期间是否能通过增强抗肿瘤免疫力来强化抗GBM肿瘤效应。我们在SD大鼠中建立了颅内C6 GBM模型，并给予放疗和白藜芦醇治疗。添加白藜芦醇进一步提高了放疗GBM大鼠的体重增加、对死亡率的抑制作用以及肿瘤体积，同时减轻了脑的病理损伤。白藜芦醇增强了放疗对炎症、细胞周期和凋亡的调节作用；联合治疗还改善了Ki-67、PD-L1以及细胞周期和凋亡相关蛋白的表达。此外，联合治疗减轻了GBM大鼠的DNA损伤并诱导其G0/G1期细胞停滞，同时伴有ATM-AKT-STAT3通路相关蛋白表达的改变。而且，放疗或白藜芦醇均可提高CD3CD8T细胞和IFN-CD8T细胞的百分比，降低（CD4CD25Foxp3）/CD4T细胞的百分比，联合治疗可增强这种作用。联合治疗对CD3、Foxp3和IFN-水平的调节作用也强于单独放疗或白藜芦醇。总之，白藜芦醇通过诱导颅内C6 GBM的DNA损伤和抗肿瘤免疫增强了放疗效果。
