Yu Huidan, Song Xueyan, Yang Fan, Wang Jun, Sun Mingjian, Liu Guangxin, Ahmad Nafees, Zhou Yuanshuai, Zhang Yina, Shi Guohua, Zhang Ruobing, Liu Jianping, Jiang Xiaobing, Fu Peng, Chen Gang, Li Jingmei, Zhuang Jie, Sun Minxuan
School of Life Sciences, Changchun University of Science and Technology, Changchun, 130022, China; Jiangsu Key Laboratory of Medical Optics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, China.
Jiangsu Key Laboratory of Medical Optics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, China.
Free Radic Biol Med. 2023 Jan;194:1-11. doi: 10.1016/j.freeradbiomed.2022.11.028. Epub 2022 Nov 24.
Glioblastoma is the most lethal intracranial malignant tumor, for which the five-year overall survival rate is approximately 5%. Here we explored the therapeutic combination of vitamin C and plasma-conditioned medium on glioblastoma cells in culture and as subcutaneous or intracranial xenografts in mice. The combination treatment reduced cell viability and proliferation while promoting apoptosis, and the effects were significantly stronger than with either treatment on its own. Similar results were obtained in the two xenograft models. Vitamin C appeared to upregulate aquaporin-3 and enhance the uptake of extracellular HO, while the combination treatment increased intracellular levels of reactive oxygen species including HO and activated the JNK signaling pathway. The cytotoxic effects of the combination treatment were partially reversed by the specific JNK signaling inhibitor SP600125. Our results suggest that the combination of vitamin C and plasma-conditioned medium has therapeutic potential against glioblastoma, and they provide mechanistic insights that may help investigate this and other potential therapies in greater depth.
胶质母细胞瘤是最致命的颅内恶性肿瘤，其五年总生存率约为5%。在此，我们探讨了维生素C与血浆条件培养基对培养的胶质母细胞瘤细胞以及小鼠皮下或颅内异种移植瘤的联合治疗效果。联合治疗降低了细胞活力和增殖，同时促进了细胞凋亡，且效果明显强于单独使用任何一种治疗方法。在两种异种移植模型中均获得了类似结果。维生素C似乎上调了水通道蛋白3并增强了细胞外过氧化氢的摄取，而联合治疗增加了包括过氧化氢在内的细胞内活性氧水平并激活了JNK信号通路。联合治疗的细胞毒性作用被特异性JNK信号抑制剂SP600125部分逆转。我们的结果表明，维生素C与血浆条件培养基的联合具有抗胶质母细胞瘤的治疗潜力，并提供了可能有助于更深入研究这种及其他潜在疗法的机制性见解。
