Mycobacterial antigen Ag85B restrains Hodgkin lymphoma tumor growth by inhibiting autophagy  

作　　者：YONGFENG CHENG YIPING SHEN YUNFEI ZHANG HAILIQIGULI NURIDING XUEMEI WANG CHUNYAN FAN GULIBAHA MAIMAITI YU LIU YINGBIN YUE DANLU LI MEI YAN 

机构地区：[1]Department of Pediatrics,The First Affiliated Hospital of Xinjiang Medical University,Urumqi,830054,China [2]Division of Genetics and Genomics,Boston Children’s Hospital,Harvard Medical School,Boston,MA 02115,USA

出　　处：《Oncology Research》2025年第5期1173-1187,共15页肿瘤学研究(英文)

基　　金：supported by the Natural Science Foundation of Xinjiang Uygur Autonomous Region of China(grant number 2022D01C739);the National Natural Science Foundation of China(grant numbers 82160031,82071276);the Key Research and Development Program of Xinjiang Uyghur Autonomous Region of China(grant number 2024B03038-1).

摘　　要：Background: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.Methods: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 in vivo impact of Ag85B was studied using BALB/c Nude mice xenografted with L-428 cells.Results: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 in vitro,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.Conclusion: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.

关 键 词：Hodgkin disease Mycobacterial antigen AUTOPHAGY Protein kinase B Mitogen-activated protein kinases 

分 类 号：R733.1[医药卫生—肿瘤]