UNC0379对胶质瘤细胞增殖影响的初步探索

doi:10.3969/j.issn.1006-7795.2023.05.006

首都医科大学学报 ›› 2023, Vol. 44 ›› Issue (5): 741-746.doi: 10.3969/j.issn.1006-7795.2023.05.006

UNC0379对胶质瘤细胞增殖影响的初步探索

刘秀，李文才 ^*

郑州大学第一附属医院病理科，郑州 450052

收稿日期:2023-07-18 出版日期:2023-10-20 发布日期:2023-10-25
通讯作者: 李文才 E-mail:liwencaipatho@126.com
基金资助:
国家自然科学基金项目（82170184），河南省医学科技攻关计划（联合共建）项目（LHGJ20220401）

Preliminary study on the effect of UNC0379 on the proliferation of glioma cells

Liu Xiu, Li Wencai^*

Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China

Received:2023-07-18 Online:2023-10-20 Published:2023-10-25
Supported by:
This study was supported by National Natural Science Foundation of China (82170184), Medical Science and Technology Research Project of Henan Province (LHGJ20220401).

摘要/Abstract

摘要： 目的初步探索组蛋白甲基转移酶KMT5A（lysine methyltransferase 5A）抑制剂UNC0379对胶质瘤细胞增殖的影响及作用机制。方法用UNC0379处理胶质瘤细胞系LN229，应用CCK8检测细胞的增殖情况，采用流式细胞术检测细胞凋亡和细胞周期情况；通过检测不同浓度的UNC0379和替莫唑胺单独或联合用药时的细胞增殖情况，计算药物联用评分，评估UNC0379对替莫唑胺治疗效果的影响。结果 UNC0379能够有效抑制LN229细胞的增殖（P<0.05），使G2/M期细胞比例增加，但并不引起LN229细胞的凋亡。另外，UNC0379还可增强LN229细胞对替莫唑胺的敏感性。结论 UNC0379可能通过引起细胞周期阻滞抑制胶质瘤细胞增殖，并可增强替莫唑胺的治疗效果。

关键词: 组蛋白甲基转移酶抑制剂, 胶质瘤, 细胞凋亡, 细胞周期, 替莫唑胺

Abstract: Objective To explore the effect and mechanism of UNC0379, an inhibitor of lysine methyltransferase 5A (KMT5A), on the proliferation of glioma cells. Methods LN229 cells were treated with UNC0379, then cell proliferation was detected by Cell counting kit-8 (CCK8), and cell apoptosis and cell cycle were measured by flow cytometry. Multi-drug combination response was also analyzed to evaluate the impact of UNC0379 on temozolomide efficacy in glioma cells. Results UNC0379 inhibited the proliferation of LN229 cells effectively (P<0.05). Although UNC0379 didn’t induce apoptosis in LN229 cells, the percentage of G2/M cells increased. UNC0379 also promoted the efficacy of temozolomide in LN229 cells. Conclusion UNC0379 could inhibit the proliferation of glioma cells by inducing cell cycle arrest and could also enhance temozolomide efficacy.

Key words: histone methyltransferase inhibitor, glioma, cell apoptosis, cell cycle, temozolomide

中图分类号:

R739.41

刘秀, 李文才. UNC0379对胶质瘤细胞增殖影响的初步探索[J]. 首都医科大学学报, 2023, 44(5): 741-746.

Liu Xiu, Li Wencai. Preliminary study on the effect of UNC0379 on the proliferation of glioma cells[J]. Journal of Capital Medical University, 2023, 44(5): 741-746.

参考文献

［1］Louis D N, Perry A, Wesseling P, et al. The 2021 WHO classification of tumors of the central nervous system: a summary［J］. Neuro Oncol, 2021, 23(8): 1231－1251.
［2］Ostrom Q T, Gittleman H, Truitt G, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2011－2015［J］. Neuro Oncol, 2018, 20(suppl_4): iv1－iv86.
［3］Berdasco M, Esteller M. Clinical epigenetics: seizing opportunities for translation［J］. Nat Rev Genet, 2019, 20(2): 109－127.
［4］Bates S E. Epigenetic therapies for cancer［J］. N Engl J Med, 2020, 383(7): 650－663.
［5］Lu Y J, Chan Y T, Tan H Y, et al. Epigenetic regulation in human cancer: the potential role of epi-drug in cancer therapy［J］. Mol Cancer, 2020, 19(1): 79.
［6］Shi X B, Kachirskaia I, Yamaguchi H, et al. Modulation of p53 function by SET8-mediated methylation at lysine 382［J］. Mol Cell, 2007, 27(4): 636－646.
［7］Takawa M, Cho H S, Hayami S, et al. Histone lysine methyltransferase SETD8 promotes carcinogenesis by deregulating PCNA expression［J］. Cancer Res, 2012, 72(13): 3217－3227.
［8］Veschi V, Liu Z H, Voss T C, et al. Epigenetic siRNA and chemical screens identify SETD8 inhibition as a therapeutic strategy for p53 activation in high-risk neuroblastoma［J］. Cancer Cell, 2017, 31(1): 50－63.
［9］Hanahan D. Hallmarks of cancer: new dimensions［J］. Cancer Discov, 2022, 12(1): 31－46.
［10］Phillips R E, Soshnev A A, Allis C D. Epigenomic reprogramming as a driver of malignant glioma［J］. Cancer Cell, 2020, 38(5): 647－660.
［11］Haag D, Mack N, Benites Goncalves da Silva P, et al. H3.3-K27M drives neural stem cell-specific gliomagenesis in a human iPSC-derived model［J］. Cancer Cell, 2021, 39(3): 407－422.e13.
［12］Katagi H, Louis N, Unruh D, et al. Radiosensitization by histone H3 demethylase inhibition in diffuse intrinsic pontine glioma［J］. Clin Cancer Res, 2019, 25(18): 5572－5583.
［13］Wu S M, Wang W P, Kong X D, et al. Dynamic regulation of the PR-Set7 histone methyltransferase is required for normal cell cycle progression［J］. Genes Dev, 2010, 24(22): 2531－2542.
［14］Jørgensen S, Elvers I, Trelle M B, et al. The histone methyltransferase SET8 is required for S-phase progression［J］. J Cell Biol, 2007, 179(7): 1337－1345.
［15］Strobel H, Baisch T, Fitzel R, et al. Temozolomide and other alkylating agents in glioblastoma therapy［J］. Biomedicines, 2019, 7(3): 69.
［16］Lee S Y. Temozolomide resistance in glioblastoma multiforme［J］. Genes Dis, 2016, 3(3): 198－210.

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UNC0379对胶质瘤细胞增殖影响的初步探索

Preliminary study on the effect of UNC0379 on the proliferation of glioma cells

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