奥罗星A通过调节TRIM24介导的铁死亡和TSPO途径抑制结直肠癌肿瘤生长。

He Chenghai, Weng Chunyan, Lai Zhichao, Luo Hui, Chen Kexin, Li Tangliang, Li Weimin, Li Guodong

Department of Gastroenterology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, Zhejiang Province, China.

The First Clinical Medical of Zhejiang Chinese Medicine University, Hangzhou, Zhejiang, China.

iScience. 2025 Jul 24;28(8):113196. doi: 10.1016/j.isci.2025.113196. eCollection 2025 Aug 15.

Colorectal cancer (CRC) is a common malignancy, and TRIM24, an E3 ubiquitin ligase, is a potential target for various cancers. This study found high TRIM24 expression in CRC, correlating with poor prognosis and disease progression. Oroxin A (OA) was identified as a TRIM24 inhibitor, promoting its degradation and inhibiting CRC cell proliferation, invasion, and migration . OA treatment linked to ferroptosis-related protein SLC3A2 and angiogenesis regulator TSPO, modulating the expression of key ferroptosis markers in a TRIM24-dependent manner. OA downregulated TRIM24, affecting TSPO ubiquitination and suppressing angiogenesis. , OA inhibited CRC tumor growth with minimal toxicity. OA is a potent antitumor agent targeting TRIM24, inducing ferroptosis, and inhibiting angiogenesis.

结直肠癌（CRC）是一种常见的恶性肿瘤，E3泛素连接酶TRIM24是多种癌症的潜在靶点。本研究发现CRC中TRIM24表达较高，与预后不良和疾病进展相关。奥洛辛A（OA）被鉴定为一种TRIM24抑制剂，可促进其降解并抑制CRC细胞的增殖、侵袭和迁移。OA治疗与铁死亡相关蛋白SLC3A2和血管生成调节因子TSPO有关，以TRIM24依赖的方式调节关键铁死亡标志物的表达。OA下调TRIM24，影响TSPO泛素化并抑制血管生成。此外，OA以最小的毒性抑制CRC肿瘤生长。OA是一种靶向TRIM24、诱导铁死亡并抑制血管生成的有效抗肿瘤药物。