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山东大学学报（医学版） ›› 2017, Vol. 55 ›› Issue (9): 31-35.doi: 10.6040/j.issn.1671-7554.0.2016.1604

• 基础医学 • 上一篇    下一篇

MnSOD乙酰化对肾透明细胞癌786-O细胞增殖、凋亡的影响

赵作辉1,2,李翠玲2,王道光2,王风芹2,曲宏懿1,丁森泰3,巩晶2,吕家驹3,杨静华2   

  1. 1.山东大学附属千佛山医院小儿外科, 山东 济南 250014;2.山东大学齐鲁医学部基础医学院癌症研究中心, 山东 济南 250012;3.山东大学附属省立医院泌尿外科, 山东 济南 250021
  • 收稿日期:2016-12-02 出版日期:2017-09-10 发布日期:2017-09-10
  • 通讯作者: 吕家驹. E-mail:kyoto2310@sina.com杨静华. E-mail:jyang@bu.edu E-mail:kyoto2310@sina.com
  • 基金资助:
    山东省科技重大专项(2015ZDXX0802A02);山东省医药卫生科技发展计划(2016WS0481)

Effect of MnSOD acetylation on the proliferation and apoptosis of clear cell renal cell carcinoma cell line 786-O

ZHAO Zuohui1,2, LI Cuiling2, WANG Daoguang2, WANG Fengqin2, QU Hongyi1, DING Sentai3, GONG Jing2, LÜ Jiaju3, YANG Jinghua2   

  1. 1. Department of Pediatrics, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, Shandong, China;
    2. Cancer Research Center, School of Basic Medicine, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China;
    3. Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China
  • Received:2016-12-02 Online:2017-09-10 Published:2017-09-10

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摘要： 目的 探讨沉默信息调节因子2-相关酶3(SIRT 3)对肾透明细胞癌细胞系786-O中锰型超氧化物歧化酶(MnSOD)的去乙酰化作用及其对786-O细胞增殖、凋亡的影响。 方法 Western blotting和免疫共沉淀(IP)测定786-O中MnSOD乙酰化的水平;MnSOD酶活性试剂盒、四甲基偶氮唑盐(MTT)和Hoechst荧光染色分别检测肾癌细胞中MnSOD酶活性、细胞增殖和凋亡。 结果 与空白载体(pcDNA3.0)相比,SIRT 3(转染pcDNA3.0-sirt3)使MnSOD乙酰化水平由1.29±0.16降低为0.74±0.07(t=7.21, P<0.001),其酶活性由(1.47±0.17)U/mg增加至(2.53±0.31)U/mg(t=6.70, P<0.001)、细胞增殖率由(25.28±5.75)%增加至(48.86±7.47)%(t=5.60, P<0.001),而细胞凋亡率由(4.53±0.51)%变为(4.45±0.59)%,差异无统计学意义(t=0.24, P=0.82)。 结论 肾透明细胞癌786-O中MnSOD的去乙酰化增强其细胞增殖能力,MnSOD或其乙酰化可能是肾透明细胞癌治疗的一个潜在靶点。

关键词: 靶向治疗, 肾透明细胞癌, 锰型超氧化物歧化酶, 去乙酰化酶, 活性氧自由基

Abstract: Objective To investigate the deacetylation of manganese superoxide dismutase(MnSOD)regulated by silent information regulator 2-related enzymes(SIRT 3)in 786-O, a clear cell renal cell carcinoma(ccRCC)cell line, and its subsequent influences on cell proliferation and apoptosis viability. Methods Western blotting and immunoprecipitation 山 东 大 学 学 报 (医 学 版)55卷9期 -赵作辉,等.MnSOD乙酰化对肾透明细胞癌786-O细胞增殖、凋亡的影响 \=-(IP)were employed to confirm MnSOD acetylation in 786-O cells. Superoxide dismutase(SOD)activity kit, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay and Hoechst fluorescence staining solution were used to measure MnSOD enzymatic activity, cell proliferation and apoptosis viability, respectively. Results Compared with plasmid empty vector(pcDNA3.0), SIRT 3(pcDNA3.0-sirt3)deacetylated mitonchondrial MnSOD from 1.29±0.16 to 0.74±0.07 in 786-O cells(t=7.21, P<0.001), enhanced its enzymatic activity from(1.47±0.17)U/mg to(2.53±0.31)U/mg(t=6.70, P<0.001), increased cell proliferation rate from(25.28±5.75)% to(48.86±7.47)%(t=5.60, P<0.001), whereas cell apoptosis rate changed from(4.53±0.51)% to(4.45±0.59)%, which remained stable(t=0.24, P=0.82). Conclusion MnSOD deacetylation enhances the proliferation activity of ccRCC cell line 786-O, which indicates that MnSOD or its acetylation might be a potential therapeutic target for RCC.

Key words: Manganese superoxide dismutase, Deacetylase, Clear cell renal cell carcinoma, Reactive oxygen species, Targeted therapy

中图分类号: 

  • R737.11
[1] Zhao Z, Wu F, Ding S, et al. Label-free quantitative proteomic analysis reveals potential biomarkers and pathways in renal cell carcinoma[J]. Tumour Biol, 2015, 36(2): 939-951.
[2] Dhar SK, St Clair DK. Manganese superoxide dismutase regulation and cancer[J]. Free Radic Biol Med, 2012, 52(11-12): 2209-2222.
[3] Vidimar V, Gius D, Chakravarti D, et al. Dysfunction MnSOD leads to redox dysregulation and activity of prosurvival AKT signaling in uterine leiomyomas[J]. Sci Adv, 2016, 2(11): e1601132. doi:10.1126/sciadv.1601132.
[4] Tao R, Coleman MC, Pennington JD, et al. Sirt3-mediated deacetylation of evolutionarily conserved lysine 122 regulates MnSOD activity in response to stress[J]. Mol Cell, 2010, 40(61): 893-904.
[5] Chen Y, Zhang J, Lin Y, et al. Tumour suppressor SIRT3 deacetylates and activates manganese superoxide dismutase to scavenge ROS[J]. EMBO Reports, 2011, 12(6): 534-541.
[6] Qiu X, Brown K, Hirschey MD, et al. Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation[J]. Cell Metab, 2010, 12(6): 662-667.
[7] 赵佳,姚创利,左林,等. 冠心病患者血清同型半胱氨酸对血脂和锰超氧化物歧化酶的影响[J]. 现代检验医学杂志, 2015,30(5): 44-49. ZHAO Jia, YAO Chuangli, ZUO Lin, et al. Effects of homocysteine on blood lipid and manganese superoxide dismutase in patients with coronary heart disease[J]. J Mod Lab Med, 2015, 30(5): 44-49.
[8] Ding S, Zhao Z, Sun D, et al. Eg5 inhibitor, a novel potent targeted therapy, induces cell apoptosis in renal cell carcinoma[J]. Tumour Biol, 2014, 35(8): 7659-7668.
[9] Hemachandra LP, Shin DH, Dier U, et al. Mitochondrial superoxide dismutase has a protumorigenic role in ovarian clear cell carcinoma[J]. Cancer Res, 2015, 75(22): 4973-4984.
[10] Pandit H, Zhang W, Li Y, et al. Manganese superoxide dismutase expression is negatively associated with microRNA-301a in human pancreatic ductal adenocarcinoma[J]. Cancer Gene Ther, 2015, 22(10): 481-486.
[11] Cui Y, Qin L, Wu J, et al. SIRT3 enhances glycolysis and proliferation in SIRT3-expressing gastric cancer cells[J]. PLoS One, 2015, 10(6): e0129834. doi: 10.1371/journal.pone.0129834.
[12] Huang P, Feng L, Oldham EA, et al. Superoxide dismutase as a target for the selective killing of cancer cells[J]. Nature, 2000, 407(6802): 390-395.
[13] Sun GG, Hu WN, Wang YD, et al. Bidirectional regulation of manganese superoxide dismutase(MnSOD)on the radiosensitivity of esophageal cancer cells[J]. Asian Pac J of Cancer Prev, 2012, 13(7): 3015-3023.
[14] Wang S, Shu J, Chen L, et al. Synergistic suppression effect on tumor growth of ovarian cancer by combining cisplatin with a manganese superoxide dismutase-armed oncolytic adenovirus[J]. Onco Targets Ther, 2016, 9: 6381-6388. doi:10.2147/OTT.S113014.
[15] Park KC, Heo JH, Jeon JY, et al. The novel histone deacetylase inhibitor, N-hydroxy-7-(2-naphthylthio)hepatonomide, exhibits potent antitumor activity due to cytochrome-c-release-mediated apoptosis in renal cell carcinoma cells[J]. BMC Cancer, 2015, 15(1): 19. doi: 10.1186/s12885-014-1003-1.
[16] Ramakrishnan S, Ellis L, Pili R. Histone modifications: implications in renal cell carcinoma[J]. Epigenomics, 2013, 5(4): 453-462.
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