Department of Respiratory and Infectious Disease of Geriatrics, The First Hospital of China Medical University, 110001, Shenyang, China.
Department of Medical Oncology, Chongqing University Cancer Hospital, Chongqing, China.
Cell Death Dis. 2023 Sep 20;14(9):617. doi: 10.1038/s41419-023-06142-y.
Aldehyde dehydrogenase 3A1 (ALDH3A1) is an NAD-dependent enzyme that is closely related to tumor development. However, its role in non-small-cell lung cancer (NSCLC) has not been elucidated. This study aimed to clarify the mechanism of ALDH3A1 and identify potential therapeutic targets for NSCLC. Here, for the first time, we found that ALDH3A1 expression could be induced by a hypoxic environment in NSCLC. ALDH3A1 was highly expressed in NSCLC tissue, especially in some late-stage patients, and was associated with a poor prognosis. In mechanistic terms, ALDH3A1 enhances glycolysis and suppresses oxidative phosphorylation (OXPHOS) to promote cell proliferation by activating the HIF-1α/LDHA pathway in NSCLC. In addition, the results showed that ALDH3A1 was a target of β-elemene. ALDH3A1 can be downregulated by β-elemene to inhibit glycolysis and enhance OXPHOS, thus suppressing NSCLC proliferation in vitro and in vivo. In conclusion, hypoxia-induced ALDH3A1 is related to the energy metabolic status of tumors and the efficacy of β-elemene, providing a new theoretical basis for better clinical applications in NSCLC.
醛脱氢酶 3A1（ALDH3A1）是一种 NAD 依赖性酶，与肿瘤的发生发展密切相关。然而，其在非小细胞肺癌（NSCLC）中的作用尚未阐明。本研究旨在阐明 ALDH3A1 的作用机制，并为 NSCLC 寻找潜在的治疗靶点。在这里，我们首次发现 ALDH3A1 的表达可被 NSCLC 中的低氧环境诱导。ALDH3A1 在 NSCLC 组织中高表达，尤其是在一些晚期患者中，与预后不良相关。从机制上讲，ALDH3A1 通过激活 HIF-1α/LDHA 通路增强糖酵解并抑制氧化磷酸化（OXPHOS），从而促进 NSCLC 细胞的增殖。此外，研究结果表明 ALDH3A1 是β-榄香烯的作用靶点。β-榄香烯可以下调 ALDH3A1，抑制糖酵解并增强 OXPHOS，从而抑制 NSCLC 的体外和体内增殖。总之，低氧诱导的 ALDH3A1 与肿瘤的能量代谢状态和β-榄香烯的疗效有关，为 NSCLC 的更好临床应用提供了新的理论依据。
