Purinergic Signalling

Purinergic signaling and tumor microenvironment in cervical Cancer

Cervical cancer is the fourth most common type of cancer incidence in the world female population, and it has become a public health problem worldwide. Several factors are involved in this type of cancer, including intrinsic factors related to the inflammatory process, such as extracellular nucleotides and adenosine-components of the purinergic system. The present review focuses on the role of the purinergic system in cervical cancer, especially regarding the interaction of extracellular nucleotides with their respective receptors expressed in the tumor microenvironment of cervical cancer and their role in the host immune response. The high concentrations of extracellular nucleotides in the tumor microenvironment of cervical cancer interfere in the regulation, proliferation, differentiation, and apoptosis of cancer cells of the uterine cervix through different P1 and P2 receptor subtypes. Such diverse cellular processes that are mediated by adenosine triphosphate and adenosine across the tumor microenvironment and that also have effects on host immune defense will be reviewed here in detail.

P2X7 receptor mediates the anti-tumor effect of running on cervical cancer in mice

Abstract Previous studies have suggested that running exerts anti-tumor effects on various cancers through multiple pathways. It has been reported that the P2X7 receptor (P2X7R) may display anti-tumor activity in cervical cancer cells, and running can regulate P2X7R expression and function in mice. However, the specific impact of running on cervical cancer and whether its underlying mechanism is associated with the regulation of P2X7R levels remains to be elucidated. In this study, mice bearing U14 cervical cancer tumors were used as a model to explore the association between running and P2X7R in cervical cancer. The results showed that running significantly inhibited tumor progression in mice, accompanied by an increase in P2X7R protein expression in tumor tissues. Additionally, treatment with the P2X7R antagonist JNJ-47965567 alone or in combination with running intervention promoted tumor growth and attenuated the anti-tumor effect of running. In contrast, the P2X7R agonist BzATP alone or combined with running intervention exerted anti-tumor effects and enhanced the anti-tumor effect of running. In conclusion, the present findings suggest only a pharmacological association between P2X7R and the anti-tumor effect of running against cervical cancer progression, given that genetic validation was not performed in this study. The potential involvement of immune mechanisms remains an inference and requires further experimental validation. As a possible therapeutic target, P2X7R provides supportive data for the treatment of cervical cancer and the clinical exploration of running as an adjuvant intervention.

P2X7 receptor involved in antitumor activity of atractylenolide I in human cervical cancer cells

Abstract Atractylenolide I (Atr-I) was found to sensitize a variety of human cancer cells in previous studies. Purinergic P2X7R plays important role in different cancers. However, whether Atr-I could generate antitumor activity in human cervical cancer cells and P2X7R get involved in this effect remain unclear. In this study, Hela (HPV 18 +) and SiHa (HPV 16 +) cells were treated with different doses of Atr-I. The results indicated that agonist and antagonist of P2X7 receptors, BzATP and JNJ-47965567 (JNJ), could suppress the proliferation of Hela and SiHa cells. Atr-I demonstrated a considerable antitumor effect in both human cervical cancer cells in vitro. Atr-I combined with P2X7R agonist, BzATP, restored Atr-I-induced growth inhibition in Hela cells but not in SiHa cells. However, the combinatorial treatment of P2X7R antagonist JNJ and Atr-I has an additive effect on cell growth inhibition in SiHa cells rather than in Hela cells. It implied that P2X7R would get involved in the anti-human cervical cancer cells effect of Atr-I.

Metastasis and angiogenesis in cervical cancer: key aspects of purinergic signaling in platelets and possible therapeutic targets

Cervical cancer ranks as the fourth most common and fatal cancer among women worldwide. Studies have demonstrated a strong association between purinergic platelet signaling and tumor progression in this type of cancer. The literature shows that neoplastic cells, when in the bloodstream, secrete adenosine triphosphate (ATP) and adenosine nucleotide diphosphate (ADP) that act on their corresponding platelet P2Y and P2X receptors. The interaction of these nucleotides with their receptors results in platelet activation and degranulation, ensuing several consequences, such as vascular endothelial growth factor (VEGF), platelet-derived growth factor, matrix metalloproteinases, ADP, and ATP. These molecules play essential roles in angiogenesis and tumor metastasis in cervical cancer. Several purinergic receptors are found in endothelial cells. Their activation, especially P2Y2, by the nucleotides released by platelets can induce relaxation of the endothelial barrier and consequent extravasation of tumor cells, promoting the development of metastases. Cancer cells that enter the bloodstream during the metastatic process are also subject to high shear stress and immune surveillance. In this context, activated platelets bind to circulating tumor cells and protect them against shear stress and the host's immune system, especially against natural killer cells, facilitating their spread throughout the body. Furthermore, activation of the P2Y12 receptor present on the platelet surface promotes the release of VEGF, the main inducer of angiogenesis in cervical cancer, in addition to increasing the concentration of several other pro-angiogenic molecules. Therefore, this review will address the role of platelet purinergic signaling in tumor progression of cervical cancer and propose possible therapeutic targets.