Department of Clinical and Experimental Medicine, Pharmacology Unit, University of Ferrara, Ferrara, Italy.
PLoS One. 2012;7(6):e39317. doi: 10.1371/journal.pone.0039317. Epub 2012 Jun 25.
A(3) adenosine receptors (ARs) play a pivotal role in the development of cancer and their activation is involved in the inhibition of tumor growth. The effects of pulsed electromagnetic fields (PEMFs) on cancer have been controversially discussed and the detailed mechanisms are not yet fully understood. In the past we have demonstrated that PEMFs increased A(2A) and A(3)AR density and functionality in human neutrophils, human and bovine synoviocytes, and bovine chondrocytes. In the same cells, PEMF exposure increased the anti-inflammatory effect mediated by A(2A) and/or A(3)ARs. The primary aim of the present study was to evaluate if PEMF exposure potentiated the anti-tumor effect of A(3)ARs in PC12 rat adrenal pheochromocytoma and U87MG human glioblastoma cell lines in comparison with rat cortical neurons. Saturation binding assays and mRNA analysis revealed that PEMF exposure up-regulated A(2A) and A(3)ARs that are well coupled to adenylate cyclase activity and cAMP production. The activation of A(2A) and A(3)ARs resulted in the decrease of nuclear factor-kappa B (NF-kB) levels in tumor cells, whilst only A(3)ARs are involved in the increase of p53 expression. A(3)AR stimulation mediated an inhibition of tumor cell proliferation evaluated by thymidine incorporation. An increase of cytotoxicity by lactate dehydrogenase (LDH) release and apoptosis by caspase-3 activation in PC12 and U87MG cells, but not in cortical neurons, was observed following A(3)AR activation. The effect of the A(3)AR agonist in tumor cells was enhanced in the presence of PEMFs and blocked by using a well-known selective antagonist. Together these results demonstrated that PEMF exposure significantly increases the anti-tumor effect modulated by A(3)ARs.
A(3) 腺苷受体 (ARs) 在癌症的发展中起着关键作用，其激活参与了肿瘤生长的抑制。脉冲电磁场 (PEMFs) 对癌症的影响一直存在争议，其详细机制尚未完全了解。过去我们已经证明，PEMFs 增加了人中性粒细胞、人滑膜细胞和牛软骨细胞中的 A(2A) 和 A(3)AR 密度和功能。在相同的细胞中，PEMF 暴露增加了由 A(2A) 和/或 A(3)AR 介导的抗炎作用。本研究的主要目的是评估 PEMF 暴露是否增强了 A(3)AR 在 PC12 大鼠肾上腺嗜铬细胞瘤和 U87MG 人神经胶质瘤细胞系中的抗肿瘤作用，与大鼠皮质神经元相比。饱和结合分析和 mRNA 分析显示，PEMF 暴露上调了 A(2A) 和 A(3)AR，它们与腺苷酸环化酶活性和 cAMP 产生良好偶联。A(2A) 和 A(3)AR 的激活导致肿瘤细胞中核因子-κB (NF-κB) 水平降低，而只有 A(3)AR 参与 p53 表达的增加。通过胸苷掺入评估，A(3)AR 刺激介导了肿瘤细胞增殖的抑制。在 PC12 和 U87MG 细胞中观察到乳酸脱氢酶 (LDH) 释放和 caspase-3 激活介导的细胞毒性增加以及细胞凋亡，但在皮质神经元中没有观察到，这是由于 A(3)AR 激活所致。在 PEMFs 存在下，A(3)AR 激动剂对肿瘤细胞的作用增强，并使用已知的选择性拮抗剂阻断。这些结果表明，PEMF 暴露显著增加了由 A(3)AR 调节的抗肿瘤作用。
