P2X7受體是ATP門控的離子通道,，其具有細(xì)胞毒活性,。然而最近的一項(xiàng)研究表明P2X7受體在腫瘤細(xì)胞增殖中發(fā)揮重要作用。
最新刊登在Cancer Research雜志上的一則研究發(fā)現(xiàn)體內(nèi)P2X7受體的存在能顯著促進(jìn)腫瘤的生長(zhǎng),。體內(nèi)研究發(fā)現(xiàn)與正常對(duì)照細(xì)胞相比,，人類胚胎腎細(xì)胞表達(dá)P2X7受體表現(xiàn)出更強(qiáng)大的成瘤性，未分化癌表型也更明顯,。瘤內(nèi)注射P2X7受體抑制劑氧化型ATP能顯著減少腫瘤增長(zhǎng)率和腫瘤體積大小,。
表達(dá)P2X7受體的腫瘤生長(zhǎng)加速是通過(guò)細(xì)胞增殖增加,、細(xì)胞凋亡減少以及高水平的轉(zhuǎn)錄因子NFATc1活化來(lái)實(shí)現(xiàn)的。與比正常腫瘤細(xì)胞相比,，高表達(dá)的腫瘤細(xì)胞形成的血管網(wǎng)以及分泌血管內(nèi)皮生長(zhǎng)因子也升高,。瘤內(nèi)注射阻斷血管內(nèi)皮生長(zhǎng)因子抗體阿瓦斯丁（貝伐單抗）或體內(nèi)沉默P2X7受體阻斷P2X7受體,，能抑制表達(dá)P2X7受體的腫瘤細(xì)胞生長(zhǎng)和血管生成。免疫組織化學(xué)顯示,，在多種人癌癥類型中P2X7受體都呈陽(yáng)性表達(dá),。
總之，研究結(jié)果表明P2X7受體在體內(nèi)能促進(jìn)腫瘤的生長(zhǎng),。（生物谷：Bioon.com）
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.
