Effective cancer therapy with limited adverse effects is a major challenge in the medical field. This is especially complicated by the development of acquired chemoresistance. Understanding the mechanisms that underlie these processes remains a major effort in cancer research. In this review, we focus on the dual role that Bid protein plays in apoptotic cell death via the mitochondrial pathway, in oncogenesis and in cancer therapeutics. The BH3 domain in Bid and the anti-apoptotic mitochondrial proteins (Bcl-2, Bcl-XL, mitochondrial ATR) it associates with at the outer mitochondrial membrane provides us with a viable target in cancer therapy. We will discuss the roles of Bid, mitochondrial ATR, and other anti-apoptotic proteins in intrinsic apoptosis, exploring how their interaction sustains cellular viability despite the initiation of upstream death signals. The unexpected upregulation of this Bid protein in cancer cells can also be instrumental in explaining the mechanisms behind acquired chemoresistance. The stable protein associations at the mitochondria between tBid and anti-apoptotic mitochondrial ATR play a crucial role in maintaining the viability of cancer cells, suggesting a novel mechanism to induce cancer cell apoptosis by freeing tBid from the ATR associations at mitochondria.
在医学领域中，实现疗效显著且副作用有限的癌症治疗是一项重大挑战，而获得性化疗耐药的出现使这一问题更为复杂。揭示这些现象背后的机制始终是癌症研究的核心课题。本综述聚焦于Bid蛋白通过线粒体途径在细胞凋亡、肿瘤发生及癌症治疗中发挥的双重作用。Bid蛋白的BH3结构域及其在线粒体外膜上与抗凋亡线粒体蛋白（Bcl-2、Bcl-XL、线粒体ATR）的结合位点，为癌症治疗提供了可行靶点。我们将系统阐述Bid、线粒体ATR及其他抗凋亡蛋白在内源性凋亡通路中的作用，深入探讨这些蛋白如何通过相互作用在死亡信号激活状态下维持细胞存活。值得注意的是，癌细胞中Bid蛋白的异常高表达现象，为阐释获得性化疗耐药机制提供了关键线索。tBid与线粒体ATR在线粒体上形成的稳定蛋白复合物对维持癌细胞存活具有决定性作用，这提示通过解离线粒体上tBid-ATR复合物以诱导癌细胞凋亡可能成为新型治疗策略。
肿瘤(癌症)患者之家