芳香苷A靶向USP8调控LXRβ介导的脂肪酸代谢重编程抗结直肠癌，这一成果由澳门大学陆金健小组经过不懈努力而取得。2026年7月8日，国际知名学术期刊《中国药理学报》发表了这一成果。

结直肠癌（CRC）仍然是一个重大的全球健康挑战，其特点是术后复发率高，生存结果差。本研究探讨了从夹竹桃中提取的天然化合物气味苷A （OA）的治疗潜力，主要研究了其调节CRC的脂质代谢和诱导癌细胞死亡的能力。在HT29和RKO细胞的皮下异种移植肿瘤模型中，OA在1.5毫克/公斤。机制研究表明，OA主要通过抑制脂肪酸氧化（FAO）途径，通过脂质过氧化诱导脂质积累并引发细胞死亡。线粒体FAO活性降低和FAO相关蛋白（包括CPT1A、CPT1B、CPT1C、CPT2和ACSL1）表达减少支持了这一效应。

此外，OA靶向泛素特异性肽酶8 (USP8)，促进肝脏X受体β (LXRβ)的泛素化和降解，这是脂质代谢的关键调节因子。LXRβ的下调进一步扰乱了FAO。本研究为开发OA作为一种基于天然化合物的CRC抗癌药物奠定了基础，并发现了USP8与LXRβ之间的新联系，为CRC脂质代谢提供了新的见解。

附：英文原文

Title: Targeting USP8 with odoroside A regulates LXRβ-mediated fatty acid metabolic reprogramming against colorectal cancer

Author: Chen, Yan-yan, Liu, Fang-fang, Wen, Shi-yuan, Song, Xiao-han, Ye, Zi-han, Xu, Chun-cao, Tu, Yan-bei, Huang, He, Lu, Jin-jian

Issue&Volume: 2026-07-08

Abstract: Colorectal cancer (CRC) remains a significant global health challenge, characterized by high post-surgical recurrence and poor survival outcomes. This study explores the therapeutic potential of odoroside A (OA), a natural compound derived from Nerium oleander, focusing on its ability to modulate lipid metabolism and induce cancer cell death on CRC. In a subcutaneous xenograft tumor model with HT29 and RKO cells, OA achieved inhibition ratios of 81.07% and 78.26% at a dose of 1.5mg/kg, respectively. Mechanistic insights revealed that OA induced lipid accumulation and triggered cell death through lipid peroxidation, primarily by inhibiting fatty acid oxidation (FAO) pathways. This effect was supported by decreased mitochondrial FAO activity and reduced expression of FAO-related proteins, including CPT1A, CPT1B, CPT1C, CPT2, and ACSL1. Additionally, OA targeted ubiquitin-specific peptidase 8 (USP8), promoting the ubiquitination and degradation of liver X receptor beta (LXRβ), a critical regulator of lipid metabolism. This downregulation of LXRβ further disrupted FAO. This study establishes a foundation for developing OA as a natural compound-based anticancer therapy for CRC and identifies a novel link between USP8 and LXRβ, offering new insights into lipid metabolism on CRC.

DOI: 10.1038/s41401-026-01873-y

Source: https://www.nature.com/articles/s41401-026-01873-y