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

doi:10.3969/j.issn.1006-7795.2023.05.006

Abstract

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

CLC Number:

R739.41

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.

0
/ / Recommend

Add to citation manager EndNote|Reference Manager|ProCite|BibTeX|RefWorks

URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2023.05.006

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2023/V44/I5/741

References

［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.

[1]	Zhang Shu, Wang Kai, Yang Zihao, Qiao Zhen, Li Xiaotong, Yuan Leilei, Ai Lin. Application of ¹¹C-MET PET/CT in screening isocitric dehydrogenase and 1p/19q status in supratentorial lower-grade gliomas [J]. Journal of Capital Medical University, 2022, 43(6): 826-833.
[2]	Xu Yang, Wang Kai, Chen Qiang, Ai Lin. Advances about molecular imaging of nuclear medicine in diagnosis and treatment of glioma [J]. Journal of Capital Medical University, 2022, 43(6): 880-885.
[3]	Li Chenchen, Xu Junmei, He Qianqian, Li Jiaying, Li Zhiheng, Xu Zhiqing, Yang Yutao. Phloretin inhibits oxidative stress response in LPS-stimulated BV2 microglia [J]. Journal of Capital Medical University, 2022, 43(1): 99-105.
[4]	Zhao Xiaoxiao, Yu Qiuhong, Ji Jianghuai, Wang Shijia, Wang Rendong, Li Dongguo. Identification of protein-coding genes regulated by differential DNA methylation enhancer regions in glioblastoma [J]. Journal of Capital Medical University, 2022, 43(1): 113-119.
[5]	Sun Mengxue, Wang Leiming, Teng Lianghong. Research progress on BRAF gene abnormality in glioma [J]. Journal of Capital Medical University, 2020, 41(3): 380-384.
[6]	Chen Feng, Zheng Xiaohong, Li Wenbin. Immunotherapy for the treatment of glioma [J]. Journal of Capital Medical University, 2019, 40(6): 966-971.
[7]	Yu Chunna, Jiang Bo, Li Wenbin, Chen Feng. Effects of β-hydroxybutyrate on the proliferation and glycolysis in glioma cells [J]. Journal of Capital Medical University, 2019, 40(2): 186-190.
[8]	Ma Xiangke, Yang Yang. Endovascular treatment of intracranial aneurysms: angiographic features and treatment outcome [J]. Journal of Capital Medical University, 2018, 39(6): 950-954.
[9]	Zhang Chuanbao, Jiang Tao. The Second Grade National Prize for Science and Technology Progress——the innovation and application of key technologies in the diagnosis and treatment of brain glioma [J]. Journal of Capital Medical University, 2018, 39(1): 1-5.
[10]	Zhang Wenli, Kong Fanhong, He Lu, Dong Chengya, Wang Yajie. Evaluation of biological characteristics of two u87 glioma cell lines after STR typing technique [J]. Journal of Capital Medical University, 2018, 39(1): 74-78.
[11]	Xia Pengfei, Wang Wei, Zou Liang, Ma Yingming. Efficacy and safety of modified antiplatelet preparation in patients with high on-treatment platelet reactivity after endovascular coiling for unruptured intracranial aneurysms [J]. Journal of Capital Medical University, 2018, 39(1): 143-147.
[12]	Zhao Qian, Jin Mei, Zhang Dawei, Zhao Wen, Zhang Xue, Li Gang, Ji Yuanqi, Ma Xiaoli. Clinical analysis and experience of 4 children medulloblastoma with progressive disease during treatment [J]. Journal of Capital Medical University, 2017, 38(6): 925-929.
[13]	Cao Yong;Zhang Maozhi;Tang Kai;Lin Song. Diagnosis and Treatment of Skull Mass-like Plasma Cell Myeloma:Report of 5 Cases [J]. Journal of Capital Medical University, 2008, 29(3): 340-343.
[14]	Liu Weisheng;Chen Shanwen;Zhao Jizong;Wang Shuo. Microsurgical Treatment of Aneurysms of Posterior Inferior Cerebellar Artery [J]. Journal of Capital Medical University, 2008, 29(3): 387-390.
[15]	Sun Jingyang;Ai Wei. Clinical Analysis of 16 Cases with Optic Nerve Glioma [J]. Journal of Capital Medical University, 2008, 29(3): 399-401.