P2X7 targeting inhibits growth of human mesothelioma.
P2X7 targeting inhibits growth of human mesothelioma.
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DOI：
10.18632/oncotarget.10430
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发表时间：
2016-08-02
期刊：
影响因子：
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通讯作者：
Di Virgilio F
中科院分区：
文献类型：
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作者：
Amoroso F;Salaro E;Falzoni S;Chiozzi P;Giuliani AL;Cavallesco G;Maniscalco P;Puozzo A;Bononi I;Martini F;Tognon M;Di Virgilio F
恶性胸膜间皮瘤（MPM）是一种侵袭性肿瘤难治性抗母细胞治疗。MPM细胞显示出几种遗传和生物化学缺陷，例如癌基因的过表达、抑癌基因的下调、microRNA的失调或细胞内Ca2+稳态和细胞凋亡的改变。目前还没有关于这种肿瘤中嘌呤能信号传导的信息。通过P2×7（P2RX7或P2×7R）嘌呤能受体的信号传导作为参与癌细胞死亡或增殖的途径而引起越来越多的关注。在这份报告中，我们表明，P2×7R是由MPM患者建立的三个MPM细胞系，但不是由健康受试者的间皮细胞（健康间皮细胞，HMCs）表达。MPM细胞增殖抑制体外孵育的选择性P2×7R拮抗剂的存在下，以及通过刺激与P2×7R激动剂BzATP。全身给予选择性P2×7R阻断剂AZ10606120可抑制MPM肿瘤的体内生长，无论是皮下（s.c.）或腹膜内（i.p.）。提示P2×7R可能成为间皮瘤治疗的新靶点。
Malignant pleural mesothelioma (MPM) is an aggressive tumor refractory to anti-blastic therapy. MPM cells show several genetic and biochemical defects, e.g. overexpression of oncogenes, downregulation of onco-suppressor genes, dysregulation of microRNA, or alteration of intracellular Ca2+ homeostasis and of apoptosis. No information is as yet available on purinergic signalling in this tumor. Signalling via the P2×7 (P2RX7 or P2×7R) purinergic receptor is attracting increasing attention as a pathway involved in cancer cell death or proliferation. In this report we show that the P2×7R is expressed by three MPM cell lines established from MPM patients but not by mesothelial cells from healthy subjects (healthy mesothelial cells, HMCs). MPM cell proliferation was inhibited by in vitro incubation in the presence of selective P2×7R antagonists, as well as by stimulation with the P2×7R agonist BzATP. Systemic administration of the selective P2×7R blocker AZ10606120 inhibited in vivo growth of MPM tumors whether implanted subcutaneously (s.c.) or intraperitoneally (i.p.). Our findings suggest that the P2×7R might be a novel target for the therapy of mesothelioma.