Effect of P2X7 receptor on tumorigenesis and its pharmacological properties

Biomed Pharmacother. 2020 May:125:109844. doi: 10.1016/j.biopha.2020.109844. Epub 2020 Jan 28.

Abstract

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.

Keywords: ATP; P2X7R; Tumor; Tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphate
  • Animals
  • Biomarkers
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism*
  • Disease Susceptibility*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunomodulation
  • Ion Channel Gating
  • Ligands
  • Neoplasms / etiology*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Protein Binding
  • Purinergic P2X Receptor Antagonists / chemistry
  • Purinergic P2X Receptor Antagonists / pharmacology
  • Receptors, Purinergic P2X7 / chemistry
  • Receptors, Purinergic P2X7 / genetics*
  • Receptors, Purinergic P2X7 / metabolism*
  • Signal Transduction
  • Structure-Activity Relationship
  • Tumor Microenvironment / genetics

Substances

  • Biomarkers
  • Ligands
  • Purinergic P2X Receptor Antagonists
  • Receptors, Purinergic P2X7
  • Adenosine Triphosphate