In contrast to the well-known anti-tumor mechanisms of aspirin in inducing apoptosis or autophagy, we here for the first time report oncosis induced by aspirin in tumor cells. In vitro and in vivo analysis showed that aspirin induced compromised Bcl-XL level and subsequent ATP depletion. Overexpression of CFP-Bcl-XL in Hela and A549 cells observably inhibited aspirin-induced ATP depletion and almost completely inhibited the aspirin-induced cells bubbling, while pharmacological inhibition of endogenous Bcl-XL activity by ABT-737 remarkably promoted aspirin-induced ATP depletion and cells bubbling, suggesting the key inhibitory role of Bcl-XL in aspirin-induced oncosis. Overexpression of Bax/Bad significantly promoted aspirin-induced oncosis. In addition, cells cultured in a glucose-free medium with low ATP level exhibited higher percentage of bubbling cells than the cells cultured in a glucose medium with high ATP level under aspirin treatment, indicating the important role of ATP depletion in aspirin-induced oncosis. Furthermore, caspase-3 was demonstrated to be not involved in aspirin-induced oncosis. Animal studies showed that aspirin treatment significantly inhibited tumors growth, but did not induce toxicities to mice. Collectively, aspirin inhibits tumors growth in mice and induces oncosis in which the compromised Bcl-XL and intracellular ATP depletion play a dominant role, which provides insights into the therapeutic strategy of aspirin in oncology.

中文翻译：

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阿司匹林在肿瘤细胞中诱发肿瘤。

与阿司匹林诱导凋亡或自噬的众所周知的抗肿瘤机制相反，我们在此首次报道阿司匹林在肿瘤细胞中诱导的肿瘤病。体外和体内分析表明，阿司匹林诱导受损的Bcl-XL水平和随后的ATP消耗。CFP-Bcl-XL在Hela和A549细胞中的过表达明显抑制了阿司匹林诱导的ATP消耗，几乎完全抑制了阿司匹林诱导的细胞起泡，而药理抑制ABT-737对内源性Bcl-XL活性的作用明显促进了阿司匹林诱导的ATP消耗。和细胞冒泡，提示Bcl-XL在阿司匹林诱导的肿瘤中的关键抑制作用。Bax / Bad的过表达显着促进了阿司匹林诱导的肿瘤。此外，在阿司匹林处理下，在低ATP水平的无葡萄糖培养基中培养的细胞比在高ATP水平的葡萄糖培养基中培养的细胞具有更高的起泡细胞百分比，表明ATP耗竭在阿司匹林诱导的肿瘤中具有重要作用。此外，caspase-3被证明与阿司匹林诱导的肿瘤无关。动物研究表明，阿司匹林治疗可显着抑制肿瘤生长，但不会对小鼠产生毒性。总的来说，阿司匹林抑制小鼠的肿瘤生长并诱发肿瘤，其中受损的Bcl-XL和细胞内ATP耗竭起主要作用，这为阿司匹林在肿瘤学中的治疗策略提供了见识。表明ATP耗竭在阿司匹林诱导的肿瘤中的重要作用。此外，caspase-3被证明与阿司匹林诱导的肿瘤无关。动物研究表明，阿司匹林治疗可显着抑制肿瘤生长，但不会对小鼠产生毒性。总的来说，阿司匹林抑制小鼠的肿瘤生长并诱发肿瘤，其中受损的Bcl-XL和细胞内ATP耗竭起主要作用，这为阿司匹林在肿瘤学中的治疗策略提供了见识。表明ATP耗竭在阿司匹林诱导的肿瘤中的重要作用。此外，caspase-3被证明与阿司匹林诱导的肿瘤无关。动物研究表明，阿司匹林治疗可显着抑制肿瘤生长，但不会对小鼠产生毒性。总的来说，阿司匹林抑制小鼠的肿瘤生长并诱发肿瘤，其中受损的Bcl-XL和细胞内ATP耗竭起主要作用，这为阿司匹林在肿瘤学中的治疗策略提供了见识。