针对能量代谢的化疗药物在不同类型的肿瘤中取得的效果并不理想。本研究设计了一种针对三磷酸腺苷（ATP）的RNA干扰（RNAi）方法，通过构建表达ATP结合RNA适配体的干扰质粒，显著抑制前列腺癌细胞的生长。该方法通过减少胞质ATP的可用性和破坏能量代谢的平衡，抑制了糖酵解和氧化磷酸化。进一步研究ATP适配体的作用机制，我们意外地发现它显著降低了膜离子通道和膜电位的活性，导致线粒体功能障碍，如线粒体数量减少、呼吸速率降低、线粒体膜电位和ATP产量下降。同时，ATP的不足阻碍了细胞的薄板足的形成，从而导致细胞迁移的显著减少。AMP活化蛋白激酶（AMPK）和内质网激酶（ERK）磷酸化的下调以及薄板足形成减少导致细胞凋亡，同时还抑制了血管生成和侵袭。综上所述，作为针对ATP消耗阻断的首个RNAi方法，本研究的方法可以干扰呼吸链和ATP库，为肿瘤治疗提供了新的途径。

Chemotherapeutic agents targeting energy metabolism have not achieved satisfactory results in different types of tumors. Herein, we developed an RNA interference (RNAi) method against adenosine triphosphate (ATP) by constructing an interfering plasmid-expressing ATP-binding RNA aptamer, which notably inhibited the growth of prostate cancer cells through diminishing the availability of cytoplasmic ATP and impairing the homeostasis of energy metabolism, and both glycolysis and oxidative phosphorylation were suppressed after RNAi treatment. Further identifying the mechanism underlying the effects of ATP aptamer, we surprisingly found that it markedly reduced the activity of membrane ionic channels and membrane potential which led to the dysfunction of mitochondria, such as the decrease of mitochondrial number, reduction in the respiration rate, and decline of mitochondrial membrane potential and ATP production. Meanwhile, the shortage of ATP impeded the formation of lamellipodia that are essential for the movement of cells, consequently resulting in a significant reduction of cell migration. Both the downregulation of the phosphorylation of AMP-activated protein kinase (AMPK) and endoplasmic reticulum kinase (ERK) and diminishing of lamellipodium formation led to cell apoptosis as well as the inhibition of angiogenesis and invasion. In conclusion, as the first RNAi modality targeting the blocking of ATP consumption, the present method can disturb the respiratory chain and ATP pool, which provides a novel regime for tumor therapies..