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Article

Inhibiting the P2X4 Receptor Suppresses Prostate Cancer Growth In Vitro and In Vivo, Suggesting a Potential Clinical Target

by
Jiepei He
1,†,
Yuhan Zhou
1,†,
Hector M. Arredondo Carrera
1,†,
Alexandria Sprules
1,
Ramona Neagu
1,
Sayyed Amin Zarkesh
1,
Colby Eaton
1,
Jian Luo
2,
Alison Gartland
1 and
Ning Wang
1,*
1
The Mellanby Centre for Bone Research, Department of Oncology and Metabolism, The University of Sheffield, Beech Hill Road, Sheffield S10 2RX, UK
2
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China
*
Author to whom correspondence should be addressed.
†
These authors contributed equally.
Cells 2020, 9(11), 2511; https://doi.org/10.3390/cells9112511
Submission received: 12 October 2020 / Revised: 15 November 2020 / Accepted: 18 November 2020 / Published: 20 November 2020
(This article belongs to the Special Issue Purine Signaling and Metabolism in Tumors)
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Abstract

Prostate cancer (PCa) is the most frequently diagnosed cancer in men, causing considerable morbidity and mortality. The P2X4 receptor (P2X4R) is the most ubiquitously expressed P2X receptor in mammals and is positively associated with tumorigenesis in many cancer types. However, its involvement in PCa progression is less understood. We hypothesized that P2X4R activity enhanced tumour formation by PCa cells. We showed that P2X4R was the most highly expressed, functional P2 receptor in these cells using quantitative reverse transcription PCR (RT-PCR) and a calcium influx assay. The effect of inhibiting P2X4R on PCa (PC3 and C4-2B4 cells) viability, proliferation, migration, invasion, and apoptosis were examined using the selective P2XR4 antagonists 5-BDBD and PSB-12062. The results demonstrated that inhibiting P2X4R impaired the growth and mobility of PCa cells but not apoptosis. In BALB/c immunocompromised nude mice inoculated with human PC3 cells subcutaneously, 5-BDBD showed anti-tumourigenic effects. Finally, a retrospective analysis of P2RX4 expression in clinical datasets (GDS1439, GDS1746, and GDS3289) suggested that P2X4R was positively associated with PCa malignancy. These studies suggest that P2X4R has a role in enhancing PCa tumour formation and is a clinically targetable candidate for which inhibitors are already available and have the potential to suppress disease progression.
Keywords: purinergic signalling; P2X4 receptor; prostate cancer; ATP; antagonist; xenograft model; clinical datasets purinergic signalling; P2X4 receptor; prostate cancer; ATP; antagonist; xenograft model; clinical datasets
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MDPI and ACS Style

He, J.; Zhou, Y.; Arredondo Carrera, H.M.; Sprules, A.; Neagu, R.; Zarkesh, S.A.; Eaton, C.; Luo, J.; Gartland, A.; Wang, N. Inhibiting the P2X4 Receptor Suppresses Prostate Cancer Growth In Vitro and In Vivo, Suggesting a Potential Clinical Target. Cells 2020, 9, 2511. https://doi.org/10.3390/cells9112511

AMA Style

He J, Zhou Y, Arredondo Carrera HM, Sprules A, Neagu R, Zarkesh SA, Eaton C, Luo J, Gartland A, Wang N. Inhibiting the P2X4 Receptor Suppresses Prostate Cancer Growth In Vitro and In Vivo, Suggesting a Potential Clinical Target. Cells. 2020; 9(11):2511. https://doi.org/10.3390/cells9112511

Chicago/Turabian Style

He, Jiepei, Yuhan Zhou, Hector M. Arredondo Carrera, Alexandria Sprules, Ramona Neagu, Sayyed Amin Zarkesh, Colby Eaton, Jian Luo, Alison Gartland, and Ning Wang. 2020. "Inhibiting the P2X4 Receptor Suppresses Prostate Cancer Growth In Vitro and In Vivo, Suggesting a Potential Clinical Target" Cells 9, no. 11: 2511. https://doi.org/10.3390/cells9112511

APA Style

He, J., Zhou, Y., Arredondo Carrera, H. M., Sprules, A., Neagu, R., Zarkesh, S. A., Eaton, C., Luo, J., Gartland, A., & Wang, N. (2020). Inhibiting the P2X4 Receptor Suppresses Prostate Cancer Growth In Vitro and In Vivo, Suggesting a Potential Clinical Target. Cells, 9(11), 2511. https://doi.org/10.3390/cells9112511

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