{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T04:31:40Z","timestamp":1790483500740,"version":"4.1.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Human malignant pleural mesothelioma (MPM) is a rare, but aggressive tumor of the serosal cavities whose 5-year survival rate is 15%. At present, there are no effective therapies for MPM. Although recent findings suggest that A<jats:sub>3<\/jats:sub> adenosine (A<jats:sub>3<\/jats:sub>AR) and P2X7 (P2X7R) receptors can be employed as antitumoral pharmacological targets in MPM, their potential role in a combined therapy is currently unknown. The A<jats:sub>3<\/jats:sub>AR agonist Cl-IB-MECA and the P2X7 receptor antagonist AZ10606120, as a single compound or in combination, were investigated <jats:italic>in vitro<\/jats:italic> for their anti-tumor activities. Assays were carried out in MPM cell lines IST-Mes2 and MPP89 and in primary human normal mesothelial cells (HMCs), as control. Single treatment with Cl-IB-MECA reduced cell proliferation and favored a pro-apoptotic effect in both MPP89 and IST-Mes2 cell lines, whereas AZ10606120 inhibited cell proliferation and induced apoptosis in IST-Mes2, only. The combined treatment with Cl-IB-MECA and AZ10606120 reduced cell proliferation and favored apoptosis in MPP89 and IST-Mes2 cell lines, whereas no synergistic effect was detected. These data cumulatively suggest the absence of a synergistic effect in combined targeting of A<jats:sub>3<\/jats:sub> adenosine and P2X7 receptors of MPM cell lines. This study may stimulate further investigations aimed at determining new combinations of antitumor compounds and more effective therapeutic strategies against MPM.<\/jats:p>","DOI":"10.3389\/fonc.2021.679285","type":"journal-article","created":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T17:17:19Z","timestamp":1633108639000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["A3 Adenosine and P2X7 Purinergic Receptors as New Targets for an Innovative Pharmacological Therapy of Malignant Pleural Mesothelioma"],"prefix":"10.3389","volume":"11","author":[{"given":"Fabrizio","family":"Vincenzi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John 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