Cancer Res：阻断P2X7受体抑制肿瘤生长

P2X7受体是ATP门控的离子通道，其具有细胞毒活性。然而最近的一项研究表明P2X7受体在肿瘤细胞增殖中发挥重要作用。

最新刊登在Cancer Research杂志上的一则研究发现体内P2X7受体的存在能显著促进肿瘤的生长。体内研究发现与正常对照细胞相比，人类胚胎肾细胞表达P2X7受体表现出更强大的成瘤性，未分化癌表型也更明显。瘤内注射P2X7受体抑制剂氧化型ATP能显著减少肿瘤增长率和肿瘤体积大小。

表达P2X7受体的肿瘤生长加速是通过细胞增殖增加、细胞凋亡减少以及高水平的转录因子NFATc1活化来实现的。与比正常肿瘤细胞相比，高表达的肿瘤细胞形成的血管网以及分泌血管内皮生长因子也升高。瘤内注射阻断血管内皮生长因子抗体阿瓦斯丁（贝伐单抗）或体内沉默P2X7受体阻断P2X7受体，能抑制表达P2X7受体的肿瘤细胞生长和血管生成。免疫组织化学显示，在多种人癌症类型中P2X7受体都呈阳性表达。

总之，研究结果表明P2X7受体在体内能促进肿瘤的生长。

doi:10.1158/0008-5472.CAN-11-1947
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Expression of P2X7 Receptor Increases In Vivo Tumor Growth

Elena Adinolfi, Lizzia Raffaghello, Anna Lisa Giuliani, Luigi Cavazzini, Marina Capece, Paola Chiozzi, et al.

The P2X7 receptor is an ATP-gated ion channel known for its cytotoxic activity. However, recent evidence suggests a role for P2X7 in cell proliferation. Here, we found that P2X7 exhibits significant growth-promoting effects in vivo. Human embryonic kidney cells expressing P2X7 exhibited a more tumorigenic and anaplastic phenotype than control cells in vivo, and the growth rate and size of these tumors were significantly reduced by intratumoral injection of the P2X7 inhibitor–oxidized ATP. The accelerated growth of P2X7-expressing tumors was characterized by increased proliferation, reduced apoptosis, and a high level of activated transcription factor NFATc1. These tumors also showed a more developed vascular network than control tumors and secreted elevated amounts of VEGF. The growth and neoangiogenesis of P2X7-expressing tumors was blocked by intratumoral injection of the VEGF-blocking antibody Avastin (bevacizumab), pharmacologic P2X7 blockade, or P2X7 silencing in vivo. Immunohistochemistry revealed strong P2X7 positivity in several human cancers. Together, our findings provide direct evidence that P2X7 promotes tumor growth in vivo.