Xu Yong-Sheng, Xiang Jun, Lin Si-Jian
The Second Affiliated Hospital, Nanchang University, Nanchang City, 343000, Jiangxi Province, China.
Department of Rehabilitation Medicine, the Second Affiliated Hospital, Nanchang University, Nanchang City, 343000, Jiangxi Province, China.
Purinergic Signal. 2024 May 21. doi: 10.1007/s11302-024-10019-w.
Numerous studies have revealed that the ATP-gated ion channel purinergic 2X7 receptor (P2X7R) plays an important role in tumor progression and the pathogenesis of cancer pain. P2X7R requires activation by extracellular ATP to perform its regulatory role functions. During tumor development or cancer-induced pain, ATP is released from tumor cells or other cells in the tumor microenvironment (such as tumor-associated immune cells), which activates P2X7R, opens ion channels on the cell membrane, affects intracellular molecular metabolism, and regulates the activity of tumor cells. Furthermore, peripheral organs and receptors can be damaged during tumor progression, and P2X7R expression in nerve cells (such as microglia) is significantly upregulated, enhancing sensory afferent information, sensitizing the central nervous system, and inducing or exacerbating pain. These findings reveal that the ATP-P2X7R signaling axis plays a key regulatory role in the pathogenesis of tumors and cancer pain and also has a therapeutic role. Accordingly, in this study, we explored the role of P2X7R in tumors and cancer pain, discussed the pharmacological properties of inhibiting P2X7R activity (such as the use of antagonists) or blocking its expression in the treatment of tumor and cancer pain, and provided an important evidence for the treatment of both in the future.
大量研究表明,三磷酸腺苷门控离子通道嘌呤能2X7受体(P2X7R)在肿瘤进展和癌痛发病机制中发挥重要作用。P2X7R需要细胞外三磷酸腺苷(ATP)激活才能发挥其调节功能。在肿瘤发展或癌症诱发疼痛期间,ATP从肿瘤细胞或肿瘤微环境中的其他细胞(如肿瘤相关免疫细胞)释放出来,激活P2X7R,打开细胞膜上的离子通道,影响细胞内分子代谢,并调节肿瘤细胞的活性。此外,在肿瘤进展过程中,外周器官和受体可能会受损,神经细胞(如小胶质细胞)中P2X7R的表达显著上调,增强感觉传入信息,使中枢神经系统敏感化,并诱导或加剧疼痛。这些发现表明,ATP-P2X7R信号轴在肿瘤和癌痛发病机制中起关键调节作用,也具有治疗作用。因此,在本研究中,我们探讨了P2X7R在肿瘤和癌痛中的作用,讨论了抑制P2X7R活性(如使用拮抗剂)或阻断其表达在治疗肿瘤和癌痛方面的药理特性,并为未来两者的治疗提供了重要依据。