Objective To investigate the mechanism by which mycobacterial antigen 85B (Ag85B) inhibits autophagy and promotes apoptosis in Hodgkin lymphoma (HL) cells. Methods The clinical data and pathological tissue slides were retrospectively collected from 80 HL children and 30 children with reactive lymphadenopathy (control group) treated at the First Affiliated Hospital of Xinjiang Medical University. Immunohistochemical analysis was performed to assess the expression of microtubule-associated protein 1 light chain 3 (LC3), sequestosome 1 (P62/SQSTM1), and Beclin-1 in the pathological tissues of HL and control groups. Human Hodgkin lymphoma cells (HDLM-2) were divided into the HDLM-2 group and the HDLM-2+Ag85B groups (with Ag85B concentrations of 0.5, 1, 2, and 4 μg/mL). The CCK8 method was used to measure HDLM-2 cell proliferation; qRT-PCR was employed to detect the expression of LC3, P62, Beclin-1, Akt, and mTOR mRNA in cells. An apoptosis kit was used to detect cell apoptosis. Results The positive expression of LC3 and Beclin-1 in the HL group were higher than those in the control group (P<0.05), while the positive expression of P62 was lower than that in the control group (P<0.05). In stages III-IV compared to stages I-II, the positive expression of LC3 and Beclin-1 increased, while the positive expression of P62 decreased (P<0.05). Cell experiment results showed that the HDLM-2+Ag85B group had suppressed cell proliferation compared to the HDLM-2 group, with decreased mRNA expression of LC3 and Beclin-1, and increased mRNA expression of P62, PI3K, Akt, and mTOR, leading to increased cell apoptosis. Notably, when Ag85B was at a concentration of 2 μg/mL, it had the strongest effect on HDLM-2 cells after 24 hours (P<0.05). Conclusions Autophagy is enhanced in children with HL and increases with disease stage. Ag85B can inhibit the proliferation and autophagy of HL tumor cells and promote apoptosis, possibly related to the activation of the PI3K/Akt/mTOR pathway.
Key words
Hodgkin lymphoma /
Mycobacterial antigen 85B /
Autophagy /
Apoptosis /
Human Hodgkin lymphoma cell
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References
1 K?l??kap S, Bar??ta I, Ulger S, et al. Clinical features and prognostic factors of Hodgkin's lymphoma: a single center experience[J]. Balkan Med J, 2013, 30(2): 178-185. PMID: 25207097. PMCID: PMC4115978. DOI: 10.5152/balkanmedj.2012.110.
2 Jacob A, Thyagarajan B, Kumar MP, et al. Cardiovascular effects of Hodgkin's lymphoma: a review of literature[J]. J Cancer Res Clin Oncol, 2018, 144(1): 99-107. PMID: 29255934. DOI: 10.1007/s00432-017-2560-x.
3 李小秋, 李甘地, 高子芬, 等. 中国淋巴瘤亚型分布: 国内多中心性病例10002例分析[J]. 诊断学理论与实践, 2012, 11(2): 111-115. DOI: 10.3969/j.issn.1671-2870.2012.02.006.
4 杨柳青, 高海霞, 马志萍, 等. 新疆地区2443例淋巴瘤构成比及临床特征分析[J]. 新疆医学, 2021, 51(1): 13-16.
5 Cirillo M, Reinke S, Klapper W, et al. The translational science of Hodgkin lymphoma[J]. Br J Haematol, 2019, 184(1): 30-44. PMID: 30417946. DOI: 10.1111/bjh.15658.
6 Piris MA, Medeiros LJ, Chang KC. Hodgkin lymphoma: a review of pathological features and recent advances in pathogenesis[J]. Pathology, 2020, 52(1): 154-165. PMID: 31699300. DOI: 10.1016/j.pathol.2019.09.005.
7 Weniger MA, Küppers R. Molecular biology of Hodgkin lymphoma[J]. Leukemia, 2021, 35(4): 968-981. PMID: 33686198. PMCID: PMC8024192. DOI: 10.1038/s41375-021-01204-6.
8 Desai S, Ansell SM. Future directions in Hodgkin lymphoma: checkpoint inhibitors and beyond[J]. Leuk Lymphoma, 2021, 62(8): 1795-1804. PMID: 33602008. DOI: 10.1080/10428194.2021.1885667.
9 Birkenmeier K, Moll K, Newrzela S, et al. Basal autophagy is pivotal for Hodgkin and Reed-Sternberg cells' survival and growth revealing a new strategy for Hodgkin lymphoma treatment[J]. Oncotarget, 2016, 7(29): 46579-46588. PMID: 27366944. PMCID: PMC5216819. DOI: 10.18632/oncotarget.10300.
10 Guo L, Xie H, Zhang Z, et al. Fusion protein vaccine based on Ag85B and STEAP1 induces a protective immune response against prostate cancer[J]. Vaccines (Basel), 2021, 9(7): 786. PMID: 34358202. PMCID: PMC8310044. DOI: 10.3390/vaccines9070786.
11 Luo L, Zhou L, Luo L, et al. Triamcinolone acetonide induces the autophagy of Ag85B-treated WI-38 cells via SIRT1/FOXO3 pathway[J]. Allergol Immunopathol (Madr), 2023, 51(2): 27-35. PMID: 36916085. DOI: 10.15586/aei.v51i2.775.
12 中国抗癌协会血液肿瘤专业委员会, 中华医学会血液学分会, 中国霍奇金淋巴瘤工作组. 中国霍奇金淋巴瘤的诊断与治疗指南（2022年版）[J]. 中华血液学杂志, 2022, 43(9): 705-715. PMID: 36709163. PMCID: PMC9613489. DOI: 10.3760/cma.j.issn.0253-2727.2022.09.001.
13 Ansell SM. Hodgkin lymphoma: a 2020 update on diagnosis, risk-stratification, and management [J]. J Hematol, 2020, 95(8): 978-989. PMID: 32384177. DOI: 10.1002/ajh.25856.
14 Kyriazopoulou L, Karpathiou G, Hatzimichael E, et al. Autophagy and cellular senescence in classical Hodgkin lymphoma[J]. Pathol Res Pract, 2022, 236: 153964. PMID: 35700577. DOI: 10.1016/j.prp.2022.153964.
15 Mizushima N, Komatsu M. Autophagy: renovation of cells and tissues[J]. Cell, 2011, 147(4): 728-741. PMID: 22078875. DOI: 10.1016/j.cell.2011.10.026.
16 Levy JMM, Towers CG, Thorburn A. Targeting autophagy in cancer[J]. Nat Rev Cancer, 2017, 17(9): 528-542. PMID: 28751651. PMCID: PMC5975367. DOI: 10.1038/nrc.2017.53.
17 White E. The role for autophagy in cancer[J]. J Clin Invest, 2015, 125(1): 42-46. PMID: 25654549. PMCID: PMC4382247. DOI: 10.1172/JCI73941.
18 Lin HC, Chang Y, Chen RY, et al. Epstein-Barr virus latent membrane protein-1 upregulates autophagy and promotes viability in Hodgkin lymphoma: Implications for targeted therapy[J]. Cancer Sci, 2021, 112(4): 1589-1602. PMID: 33525055. PMCID: PMC8019199. DOI: 10.1111/cas.14833.
19 Onorati AV, Dyczynski M, Ojha R, et al. Targeting autophagy in cancer[J]. Cancer, 2018, 124(16): 3307-3318. PMID: 29671878. PMCID: PMC6108917. DOI: 10.1002/cncr.31335.
20 Wang H, Liu Y, Wang D, et al. The upstream pathway of mTOR-mediated autophagy in liver diseases[J]. Cells, 2019, 8(12): 1597. PMID: 31835352. PMCID: PMC6953127. DOI: 10.3390/cells8121597.
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