The Second Affiliated Hospital, Nanchang University, Nanchang City, Jiangxi Province, 343000, China.
The Second Affiliated Hospital, Nanchang University, Nanchang City, Jiangxi Province, 343000, China.
Biomed Pharmacother. 2020 May;125:109844. doi: 10.1016/j.biopha.2020.109844. Epub 2020 Jan 28.
The occurrence and development of tumors is a multi-factor, multi-step, multi-gene pathological process, and its treatment has been the most difficult problem in the field of medicine today. Therefore, exploring the relevant factors involved in the pathogenesis of tumors, improving the diagnostic rate, treatment rate, and prognosis survival rate of tumors have become an urgent problem to be solved. A large number of studies have shown that the P2X7 receptor (P2X7R) and the tumor microenvironment play an important role in regulating the growth, apoptosis, migration and invasion of tumor cells. P2X7R is an ATP ligand-gated cationic channel receptor, which exists in most tissues of the human body. The main function of P2X7R is to regulate the relevant cells (such as macrophages, lymphocytes, and glial cells) to release damaging factors and induce apoptosis and cell death. In recent years, with continuous research and exploration of P2X7R, it has been found that P2X7R exists on the surface of most tumor cells and plays an important role in tumor pathogenesis. The activation of the P2X7R can open the ion channels on the tumor cell membrane (sodium ion, calcium ion influx and potassium ion outflow), trigger rearrangement of the cytoskeleton and changes in membrane fluidity, allow small molecule substances to enter the cell, activate enzymes and kinases in related signaling pathways in cells (such as PKA, PKC, ERK1/2, AKT, and JNK), thereby affecting the development of tumor cells, and can also indirectly affect the growth, apoptosis and migration of tumor cells through tumor microenvironment. At present, P2X7R has been widely recognized for its important role in tumorigenesis and development. In this paper, we give a comprehensive description of the structure and function of the P2X7R gene. We also clarified the concept of tumor microenvironment and its effect on tumors, discussed the relevant pathological mechanisms in the development of tumors, and revealed the intrinsic relationship between P2X7R and tumors. We explored the pharmacological properties of P2X7R antagonists or inhibitors in reducing its expression as targeted therapy for tumors.
肿瘤的发生发展是一个多因素、多步骤、多基因的病理过程，其治疗一直是当今医学领域最困难的问题。因此，探索肿瘤发病机制中涉及的相关因素，提高肿瘤的诊断率、治疗率和预后生存率已成为亟待解决的问题。大量研究表明，P2X7 受体（P2X7R）与肿瘤微环境在调节肿瘤细胞的生长、凋亡、迁移和侵袭中发挥重要作用。P2X7R 是一种 ATP 配体门控阳离子通道受体，存在于人体大多数组织中。P2X7R 的主要功能是调节相关细胞（如巨噬细胞、淋巴细胞和神经胶质细胞）释放损伤因子，并诱导细胞凋亡和死亡。近年来，随着对 P2X7R 的不断研究和探索，发现 P2X7R 存在于大多数肿瘤细胞表面，在肿瘤发病机制中发挥重要作用。P2X7R 的激活可以打开肿瘤细胞膜上的离子通道（钠离子、钙离子内流和钾离子外流），触发细胞骨架重排和膜流动性变化，使小分子物质进入细胞，激活细胞内相关信号通路中的酶和激酶（如 PKA、PKC、ERK1/2、AKT 和 JNK），从而影响肿瘤细胞的发展，还可以通过肿瘤微环境间接影响肿瘤细胞的生长、凋亡和迁移。目前，P2X7R 因其在肿瘤发生和发展中的重要作用而得到广泛认可。本文对 P2X7R 基因的结构和功能进行了全面描述。还阐明了肿瘤微环境的概念及其对肿瘤的影响，讨论了肿瘤发生发展过程中的相关病理机制，揭示了 P2X7R 与肿瘤之间的内在联系。探讨了 P2X7R 拮抗剂或抑制剂降低其表达作为肿瘤靶向治疗的药理学特性。
