Brain metastasis is a leading cause of death worldwide, but the mechanism involved remains unclear. Stromal cell-derived factor-1 (SDF-1)/C-X-C motif chemokine receptor 4 (CXCR4) signaling has been reported to induce the directed metastasis of cancers, and adenosine A2A receptor activation suppresses the SDF-1/CXCR4 interaction. However, whether A2A receptor activation implicates the SDF-1/CXCR4 signaling pathway and thus modulates brain metastasis remains unclear. In this study, Western blot was performed to evaluate the protein levels. Cell invasion and migration assays were used to estimate the metastasis ability of PC-9 cells. The viability of cells was demonstrated by lactate dehydrogenase and cell proliferation assays. And the findings in vitro were further identified in nude mice. Notably, adenosine A2A receptor activation inhibited the proliferation and viability of PC-9 cells and thus suppressed the brain metastasis. A2A receptor stimulation protected the function of blood-brain barrier (BBB). The suppression of brain metastasis and the protection of BBB by A2A receptor relied on SDF-1/CXCR4 signaling, and treatment using A2A receptor agonist and CXCR4 antagonist protected the nude mice from malignancy metastasis in vivo. Adenosine A2A receptor activation suppressed the brain metastasis by implicating the SDF-1/CXCR4 axis and protecting the BBB.

中文翻译：

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腺苷A2A受体激活通过SDF-1 / CXCR4轴减少脑转移并保护血脑屏障。

脑转移是全球范围内主要的死亡原因，但其机制尚不清楚。据报道，基质细胞衍生因子-1（SDF-1）/ CXC基序趋化因子受体4（CXCR4）信号可诱导癌症的定向转移，而腺苷A2A受体激活可抑制SDF-1 / CXCR4相互作用。但是，尚不清楚A2A受体激活是否牵涉SDF-1 / CXCR4信号传导途径并因此调节脑转移。在这项研究中，进行了蛋白质印迹法以评估蛋白质水平。细胞侵袭和迁移测定用于估计PC-9细胞的转移能力。乳酸脱氢酶和细胞增殖试验证明了细胞的活力。并在裸鼠中进一步鉴定了体外发现。值得注意的是 腺苷A2A受体激活抑制PC-9细胞的增殖和活力，从而抑制脑转移。A2A受体刺激保护了血脑屏障（BBB）的功能。A2A受体对脑转移的抑制和对BBB的保护依赖于SDF-1 / CXCR4信号传导，使用A2A受体激动剂和CXCR4拮抗剂进行的治疗可保护裸鼠免于体内恶性转移。腺苷A2A受体激活通过牵涉SDF-1 / CXCR4轴并保护BBB抑制了脑转移。使用A2A受体激动剂和CXCR4拮抗剂进行的治疗可以保护裸鼠免于体内恶性转移。腺苷A2A受体激活通过牵涉SDF-1 / CXCR4轴并保护BBB抑制了脑转移。使用A2A受体激动剂和CXCR4拮抗剂进行的治疗可以保护裸鼠免于体内恶性转移。腺苷A2A受体激活通过牵涉SDF-1 / CXCR4轴并保护BBB抑制了脑转移。