中国肿瘤外科杂志2025，Vol.17Issue(3)：241-247,7.DOI:10.3969/j.issn.1674-4136.2025.03.006
Ag85B通过PI3K/AKT/mTOR通路抑制霍奇金淋巴瘤细胞自噬并促进凋亡
Ag85B inhibits autophagy and promotes apoptosis in Hodgkin lymphoma cells via the PI3K/AKT/mTOR pathway
摘要
Abstract
Objective To investigate the effect of Mycobacterium tuberculosis antigen Ag85B on autophagy and apoptosis in Hodgkin lymphoma(HL)cells,and to explore the underlying mechanisms.Methods Human HL cells(L-428)were divided into five groups:L-428,L-428+Ag85B(Ag85B at concentrations of 1,2,4,and 8 μg/mL).Western blot was used to detect the expression of LC3,p62,Beclin-1,ATG14,PI3K,AKT,mTOR,p-PI3K,p-AKT,p-mTOR,PARP,and Cleaved caspase-8 proteins in the cells.Apoptosis was measured using an apoptosis kit,and cell cycle distribution was analyzed by flow cytometry.Autophagic vesicles were observed by transmission electron microscopy(TEM).qRT-PCR was performed to measure mRNA levels of LC3,Beclin-1,and caspase-8.Results The expression of LC3 protein in the L-428+Ag85B groups was lower than in the L-428 group,and p62 expression was higher,with the most significant difference observed at 4 μg/mL Ag85B(P＜0.05).Western blot analysis showed that in the Ag85B-treated groups,the phosphorylation protein expression ratio of p-PI3K/PI3K,p-AKT/AKT,and p-mTOR/mTOR was higher than in the control group,while LC3,Beclin-1,and ATG14 expression levels were lower(P＜0.05).TEM images revealed reduced autophagosome formation in Ag85B-treated cells.Apoptosis assays showed significantly higher early and late apoptosis rates in Ag85B-treated cells compared to controls(P＜0.05),with elevated levels of cleaved caspase-8 and PARP expression.Flow cytometry revealed cell cycle arrest at the S phase in the Ag85B group(P＜0.05).Western blot analysis showed increased expression of p-mTOR after Ag85B treatment,while co-treatment with LY294002(PI3K/AKT inhibitor)reduced p-mTOR expression,increased LC3 and Beclin-1 mRNA expression,and decreased caspase-8 mRNA expression(P＜0.05).Conclusions Ag85B inhibits autophagy and promotes apoptosis in HL tumor cells by blocking the cell cycle at the S phase.The mechanism underlying this effect involves the modulation of the PI3K/AKT/mTOR pathway.关键词
霍奇金淋巴瘤/Ag85B/自噬/凋亡/PI3K/AKT/mTORKey words
Hodgkin lymphoma/Ag85B/Autophagy/Apoptosis/PI3K/AKT/mTOR引用本文复制引用
程永凤,沈亦平,樊春艳,王学梅,余霞,古丽巴哈·买买提,贾继鹏,严媚..Ag85B通过PI3K/AKT/mTOR通路抑制霍奇金淋巴瘤细胞自噬并促进凋亡[J].中国肿瘤外科杂志,2025,17(3):241-247,7.基金项目
国家自然科学基金(82160031,82071276) （82160031,82071276）
新疆维吾尔自治区自然科学基金青年科学基金(2022D01C739) （2022D01C739）
新疆维吾尔自治区重点研发专项(2024B03038-1) （2024B03038-1）
新疆维吾尔自治区"天山英才"医药卫生高层次人才培养计划领军人才(TSYC202301A002) （TSYC202301A002）
