Extracellular nucleotides inhibit growth of human oesophageal cancer cells via P2Y(2)-receptors.
Extracellular nucleotides inhibit growth of human oesophageal cancer cells via P2Y(2)-receptors.
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DOI：
10.1038/sj.bjc.6600100
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发表时间：
2002-02-12
影响因子：
8.8
通讯作者：
Scherubl, H
中科院分区：
文献类型：
--
作者：
Maaser, K;Hopfner, M;Kap, H;Sutter, A P;Barthel, B;von Lampe, B;Zeitz, M;Scherubl, H
已知细胞外 ATP 通过激活特定的嘌呤能受体（P2 受体）来抑制各种肿瘤的生长。由于晚期食管癌的治疗效果并不令人满意，新的治疗方法势在必行。在这里，我们研究了人食管癌细胞中 P2 嘌呤能受体的功能表达和潜在的抗增殖作用。将人食管癌以及鳞状食管癌细胞系 Kyse-140 的原代细胞培养物与 ATP 或其稳定类似物 ATPγS 长时间孵育，会剂量依赖性地抑制细胞增殖。这是由于细胞凋亡的诱导和细胞周期停滞。通过 RT-PCR、免疫细胞化学和 [Ca2+]i 成像检查 P2 受体的表达。各种细胞外核苷酸的应用剂量依赖性地增加[Ca2+]i。效力的顺序为ATP=UTP>ATPγS>ADP=UDP。 2-甲硫基-ATP和α,β-亚甲基-ATP对[Ca2+]i没有影响。观察到 ATP 和 UTP 之间完全交叉脱敏。此外，磷脂酶 C 抑制剂 U73122 剂量依赖性地降低 ATP 触发的 [Ca2+]i 信号。药理学特征强烈表明 G 蛋白偶联 P2Y2 受体在食管鳞状癌细胞中的功能表达。 P2Y2 受体参与细胞外核苷酸的抗增殖作用。因此，P2Y2 受体是食管癌治疗创新方法的有前途的靶蛋白。英国癌症杂志 (2002) 86, 636–644。 DOI：10.1038/sj/bjc/6600100 www.bjcancer.com © 2002 英国癌症研究中心
Extracellular ATP is known to inhibit growth of various tumours by activating specific purinergic receptors (P2-receptors). Since the therapy of advanced oesophageal cancer is unsatisfying, new therapeutic approaches are mandatory. Here, we investigated the functional expression and potential antiproliferative effects of P2-purinergic receptors in human oesophageal cancer cells. Prolonged incubation of primary cell cultures of human oesophageal cancers as well as of the squamous oesophageal cancer cell line Kyse-140 with ATP or its stable analogue ATPγS dose-dependently inhibited cell proliferation. This was due to both an induction of apoptosis and cell cycle arrest. The expression of P2-receptors was examined by RT-PCR, immunocytochemistry, and [Ca2+]i-imaging. Application of various extracellular nucleotides dose-dependently increased [Ca2+]i. The rank order of potency was ATP=UTP>ATPγS>ADP=UDP. 2-methylthio-ATP and α,β-methylene-ATP had no effects on [Ca2+]i. Complete cross-desensitization between ATP and UTP was observed. Moreover, the phospholipase C inhibitor U73122 dose-dependently reduced the ATP triggered [Ca2+]i signal. The pharmacological features strongly suggest the functional expression of G-protein coupled P2Y2-receptors in oesophageal squamous cancer cells. P2Y2-receptors are involved in the antiproliferative actions of extracellular nucleotides. Thus, P2Y2-receptors are promising target proteins for innovative approaches in oesophageal cancer therapy. British Journal of Cancer (2002) 86, 636–644. DOI: 10.1038/sj/bjc/6600100 www.bjcancer.com © 2002 Cancer Research UK