Cheng Yongfeng, Shen Yiping, Zhang Yunfei, Nuriding Hailiqiguli, Wang Xuemei, Fan Chunyan, Maimaiti Gulibaha, Liu Y U, Yue Yingbin, Li Danlu, Yan Mei
Department of Pediatrics, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China.
Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Oncol Res. 2025 Apr 18;33(5):1173-1187. doi: 10.32604/or.2025.057842. eCollection 2025.
The growth of the B-cell lymphoma subtype, Hodgkin lymphoma (HL), is associated with increased autophagy. A mycobacterial antigen, Ag85, has been reported to inhibit cell autophagy under a variety of conditions. Whether Ag85 could inhibit autophagy in HL is unknown.
Lymph node samples from patients with HL and healthy controls were collected to assess proliferation and autophagy. The human HL cell line, L-428, was cultured and subjected to Ag85B treatment. Autophagy in L-428 cells was evaluated through western blotting analysis, immunohistochemistry, and transmission electron microscopy. Apoptosis in these cells was measured using flow cytometry and western blotting. The associated signaling pathways were also analyzed utilizing western blotting. The impact of Ag85B was studied using BALB/c Nude mice xenografted with L-428 cells.
We observed increased proliferation and autophagy in primary lymphoma tissues of patients. Administration of Ag85B inhibited the proliferation and autophagy of HL cell lines. Moreover, Ag85B promoted apoptotic pathway activation , which might be associated with mitochondrial dysfunction. Mechanistically, Ag85B inhibits autophagy by activating the phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B/mechanistic target of rapamycin kinase (PI3K/AKT/mTOR) and mitogen-activated protein kinase (MAPK) pathways. Ag85B also inhibited lymphoma growth in mice xenografted with HL cell lines, but no potential toxicity was observed.
Altogether, these results suggest that Ag85B inhibits HL growth via autophagy regulation. Current treatments for HL are associated with adverse events; therefore, Ag85B-mediated autophagy inhibition might be a promising strategy in to treat HL.
B细胞淋巴瘤亚型霍奇金淋巴瘤（HL）的生长与自噬增加有关。据报道，一种分枝杆菌抗原Ag85在多种条件下可抑制细胞自噬。Ag85是否能抑制HL中的自噬尚不清楚。
收集HL患者和健康对照者的淋巴结样本，以评估增殖和自噬情况。培养人HL细胞系L-428，并进行Ag85B处理。通过蛋白质印迹分析、免疫组织化学和透射电子显微镜评估L-428细胞中的自噬。使用流式细胞术和蛋白质印迹法检测这些细胞中的凋亡情况。还利用蛋白质印迹法分析相关信号通路。使用接种L-428细胞的BALB/c裸鼠研究Ag85B的作用。
我们观察到患者原发性淋巴瘤组织中的增殖和自噬增加。给予Ag85B可抑制HL细胞系的增殖和自噬。此外，Ag85B促进凋亡途径激活，这可能与线粒体功能障碍有关。机制上，Ag85B通过激活磷脂酰肌醇-4,5-二磷酸3-激酶/蛋白激酶B/雷帕霉素激酶机制靶点（PI3K/AKT/mTOR）和丝裂原活化蛋白激酶（MAPK）途径来抑制自噬。Ag85B还抑制了接种HL细胞系的小鼠体内淋巴瘤的生长，但未观察到潜在毒性。
总之，这些结果表明Ag85B通过自噬调节抑制HL生长。目前HL的治疗与不良事件相关；因此，Ag85B介导的自噬抑制可能是治疗HL的一种有前景的策略。
