Vincenzi Fabrizio, Rotondo John Charles, Pasquini Silvia, Di Virgilio Francesco, Varani Katia, Tognon Mauro
Department of Translational Medicine, Pharmacology Section, University of Ferrara, Ferrara, Italy.
Department of Medical Sciences, Experimental Medicine Section, Laboratories of Cell Biology and Molecular Genetics, University of Ferrara, Ferrara, Italy.
Front Oncol. 2021 Oct 1;11:679285. doi: 10.3389/fonc.2021.679285. eCollection 2021.
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 adenosine (AAR) and P2X7 (P2X7R) receptors can be employed as antitumoral pharmacological targets in MPM, their potential role in a combined therapy is currently unknown. The AAR agonist Cl-IB-MECA and the P2X7 receptor antagonist AZ10606120, as a single compound or in combination, were investigated 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 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.
人类恶性胸膜间皮瘤（MPM）是一种罕见但侵袭性强的浆膜腔肿瘤，其5年生存率为15%。目前，MPM尚无有效的治疗方法。尽管最近的研究结果表明，A1腺苷（A1AR）和P2X7（P2X7R）受体可作为MPM的抗肿瘤药理学靶点，但其在联合治疗中的潜在作用目前尚不清楚。研究了A1AR激动剂Cl-IB-MECA和P2X7受体拮抗剂AZ10606120单独或联合使用时的抗肿瘤活性。以MPM细胞系IST-Mes2和MPP89以及原代人正常间皮细胞（HMCs）作为对照进行实验。单独使用Cl-IB-MECA处理可降低MPP89和IST-Mes2细胞系的细胞增殖并促进促凋亡作用，而AZ10606120仅抑制IST-Mes2细胞系的细胞增殖并诱导其凋亡。Cl-IB-MECA和AZ10606120联合处理可降低MPP89和IST-Mes2细胞系的细胞增殖并促进凋亡，但未检测到协同效应。这些数据累积表明，联合靶向MPM细胞系的A1腺苷和P2X7受体不存在协同效应。本研究可能会激发进一步的研究，旨在确定抗肿瘤化合物的新组合以及针对MPM更有效的治疗策略。
