Xu Shuai, Liang Qi, Li Hang, Zhou Hai, Xu Zhenyuan, Yan Yanjun, Zhang Yue, Ye Renqun, You Xujun
Department of Endocrine, Shenzhen Bao'an Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, No. 25, Yuan Road, Bao'an District, Shenzhen, Guangdong, 518101, China.
Department of Pharmacy, Shenzhen Bao'an Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518101, China.
Cancer Cell Int. 2025 Jul 2;25(1):245. doi: 10.1186/s12935-025-03853-4.
Diosbulbin B (DB) is a traditional Chinese medicine used for thyroid cancer treatment, but always brings severe liver injury. In the current study, we investigated the role of astragalus polysaccharide (APS) in DB-induced hepatotoxicity and their anti-tumor effect on BRAF papillary thyroid cancer (PTC), and disclosed the underlying mechanisms.
Two BRAF PTC IHH-4 and GLAG-66 cell lines were applied for the in vitro assays. CCK-8, flow cytometry, transwell chambers, enzyme-linked immunosorbent assay (ELISA) and transmission electron microscopy (TEM) were performed for cell growth, apoptosis, migration/invasion, malondialdehyde (MDA)/glutathione (GSH) content and mitochondria damage detection. Human normal liver epithelial cell line THLE-2 was used to assess the liver toxicity, together with the animal experiment.
The IC50 of APS and DB in IHH-4 cells were 153.9 µg/mL and 41.2 µM, respectively, while they were 728.0 µg/mL and 22.74 µM in GLAG-66 cells. Combination of APS and DB enhanced the anti-cancer role of DB with increased cell apoptosis and LDH release, and weakened cell growth, migration and invasion capacities. Interestingly, the combination of these two drugs significantly alleviated the liver injury induced by DB. In mechanism, we found that APS combined with DB treatment triggered the increase of MDA level while decreased GSH level, and deteriorated mitochondria damage. Inhibition of ferroptosis impaired the anti-PTC role of APS combined with DB with no influencing on liver injury both in vivo and in vitro.
In conclusion, our study shows the combined therapy strategy of APS and DB regimen achieves better anti-cancer response through increasing MDA level while decreasing GSH level. Importantly, the combined therapy of APS and DB significantly decreased the liver toxicity induced by DB. These findings suggest that APS combined DB is a potential therapeutic strategy for BRAF PTC with high efficacy and low liver toxicity.
薯蓣皂苷元B（DB）是一种用于治疗甲状腺癌的传统中药，但常导致严重的肝损伤。在本研究中，我们探究了黄芪多糖（APS）在DB诱导的肝毒性中的作用及其对BRAF乳头状甲状腺癌（PTC）的抗肿瘤作用，并揭示了其潜在机制。
使用两种BRAF PTC细胞系IHH-4和GLAG-66进行体外实验。采用CCK-8、流式细胞术、Transwell小室、酶联免疫吸附测定（ELISA）和透射电子显微镜（TEM）检测细胞生长、凋亡、迁移/侵袭、丙二醛（MDA）/谷胱甘肽（GSH）含量及线粒体损伤情况。使用人正常肝上皮细胞系THLE-2并结合动物实验评估肝毒性。
APS和DB在IHH-4细胞中的半数抑制浓度（IC50）分别为153.9 μg/mL和41.2 μM，而在GLAG-66细胞中分别为728.0 μg/mL和22.74 μM。APS与DB联合使用增强了DB的抗癌作用，增加了细胞凋亡和乳酸脱氢酶（LDH）释放，削弱了细胞生长、迁移和侵袭能力。有趣的是，这两种药物联合使用显著减轻了DB诱导的肝损伤。机制上，我们发现APS与DB联合处理导致MDA水平升高而GSH水平降低，并加剧了线粒体损伤。抑制铁死亡削弱了APS与DB联合使用对PTC的抗癌作用，且对体内外肝损伤均无影响。
总之，我们的研究表明，APS与DB联合治疗方案通过提高MDA水平同时降低GSH水平实现了更好的抗癌反应。重要的是，APS与DB联合治疗显著降低了DB诱导的肝毒性。这些发现表明，APS联合DB是一种治疗BRAF PTC的潜在策略，具有高效和低肝毒性的特点。
