切换至 "中华医学电子期刊资源库"

中华妇幼临床医学杂志(电子版) ›› 2018, Vol. 14 ›› Issue (06) : 629 -635. doi: 10.3877/cma.j.issn.1673-5250.2018.06.002

所属专题: 文献

专家约稿

蛋白酶体抑制剂MG132对卵巢癌作用机制的研究现状
岳驰1, 刘辉2, 刘星辰2, 魏宝宝2, 郭娜2,()   
  1. 1. 610031 成都市妇女儿童中心医院妇产科
    2. 610041 成都,四川大学华西第二医院妇产科、出生缺陷与相关妇儿疾病教育部重点实验室
  • 收稿日期:2018-09-18 修回日期:2018-11-07 出版日期:2018-12-01
  • 通信作者: 郭娜

Research status on mechanism of proteasome inhibitor MG132 on ovarian cancer

Chi Yue1, Hui Liu2, Xingchen Liu2, Baobao Wei2, Na Guo2,()   

  1. 1. Department of Obstetrics and Gynecology, Chengdu Women′s and Children′s Central Hospital, Chengdu 610031, Sichuan Province, China
    2. Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
  • Received:2018-09-18 Revised:2018-11-07 Published:2018-12-01
  • Corresponding author: Na Guo
  • About author:
    Corresponding author: Guo Na, Email:
  • Supported by:
    Scientific Research Project of Health and Family Planning Commission of Sichuan Province (Universal Application Project)(16PJ236)
引用本文:

岳驰, 刘辉, 刘星辰, 魏宝宝, 郭娜. 蛋白酶体抑制剂MG132对卵巢癌作用机制的研究现状[J/OL]. 中华妇幼临床医学杂志(电子版), 2018, 14(06): 629-635.

Chi Yue, Hui Liu, Xingchen Liu, Baobao Wei, Na Guo. Research status on mechanism of proteasome inhibitor MG132 on ovarian cancer[J/OL]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2018, 14(06): 629-635.

泛素蛋白酶体途径(UPP)和自噬溶酶体途径(ALP)是真核细胞内蛋白质降解的2种重要途径。MG132是一种可逆性肽醛类蛋白酶体(proteasome)抑制剂,可进入细胞中可逆性抑制蛋白酶体活性,抑制UPP介导的蛋白质降解,从而诱导细胞凋亡。自噬性细胞死亡是一种不同于细胞凋亡的程序性死亡,细胞自噬是细胞利用溶酶体降解自身受损的大分子物质和细胞器的生理性细胞死亡过程。卵巢癌是女性生殖系统三大恶性肿瘤之一。晚期卵巢癌患者的5年生存率约为47%,是妇科恶性肿瘤中导致患者死亡率最高的肿瘤。MG132可通过调节凋亡蛋白表达,促进卵巢癌细胞凋亡,但是否可通过调控凋亡、自噬蛋白表达,促进卵巢癌细胞死亡,则迄今文献报道较少。笔者拟就蛋白酶体抑制剂MG132对卵巢癌的作用机制的最新研究现状进行阐述,旨在为MG132治疗卵巢癌提供理论基础。

The ubiquitin-proteasome pathway (UPP) and autophagy-lysosome pathway (ALP) are two major ways of protein degradation in eukaryotic cells. MG132 (Z-Leu-Leu-CHO) is a reversible peptide aldehyde proteasome inhibitor, which can enter into cells and reversibly inhibiting proteasome activities, thus inhibiting protein degradation mediated by UPP, affecting the course of cell cycle and inducing apoptosis of cells. Autophagic cell death is a type of programmed cell death different from apoptosis. Autophagy is a process of physiological cell death by using the lysosomes to degrade their own damaged macromolecules and organelles. Ovarian cancer is one of the three malignant tumors of female reproductive system. The 5-year survival rate of advanced ovarian cancer is about 47%, which is the highest mortality rate in gynecologic malignancies. It has been reported that MG132 can promote apoptosis of ovarian cancer cells by regulating the expression of apoptotic protein, but it is rare to report whether it can promote cell death of ovarian cancer cells by regulating the expression of apoptotic and autophagic protein. This review demonstrates the latest research status of mechanism of MG132 on ovarian cancer in order to provide a theoretical basis for the treatment of ovarian cancer by MG132.

[1]
Siegel RL, Miller KD, Jemal A.Cancer statistics, 2018[J]. CA Cancer J Clin, 2018, 68(1): 7-30.
[2]
Leamon CP, Lovejoy CD, Nguyen B. Patient selection and targeted treatment in the management of platinum-resistant ovarian cancer[J]. Pharmgenomics Pers Med, 2013, 6: 113-125.
[3]
Wojcik S. Crosstalk between autophagy and proteasome protein degradation systems: possible implications for cancer therapy[J]. Folia Histochem Cytobiol, 2013, 51(4): 249-264.
[4]
Ding WX, Ni HM, Gao W, et al. Linking of autophagy to ubiquitin-proteasome system is important for the regulation of endoplasmic reticulum stress and cell viability[J]. Am J Pathol, 2007, 171(2): 513-524.
[5]
Han YH, Park WH. MG132, a proteasome inhibitor decreased the growth of Calu-6 lung cancer cells via apoptosis and GSH depletion[J]. Toxicol In Vitro, 2010, 24(4): 1237-1242.
[6]
Zwickl P, Voges D, Baumeister W. The proteasome: a macromolecular assembly designed for controlled proteolysis[J]. Philos Trans R Soc Lond B Biol Sci, 1999, 354(1389): 1501-1511.
[7]
Pickart CM, Eddins MJ. Ubiquitin: structures, functions, mechanisms[J]. Biochim Biophys Acta, 2004, 1695(1-3): 55-72.
[8]
Mukhopadhyay D, Riezman H. Proteasome-independent functions of ubiquitin in endocytosis and signaling[J]. Science, 2007, 315(5809): 201-205.
[9]
Goldberg AL. Nobel committee tags ubiquitin for distinction[J]. Neuron, 2005, 45(3): 339-344.
[10]
Bai M, Zhao X, Sahara K, et al. Assembly mechanisms of specialized core particles of the proteasome[J]. Biomolecules, 2014, 4(3): 662-677.
[11]
倪晓光,赵平. 泛素-蛋白酶体途径的组成和功能[J]. 生理科学进展,2006, 37(3): 255-258.
[12]
Klionsky DJ. The molecular machinery of autophagy: unanswered questions[J]. J Cell Sci, 2005, 118(Pt 1): 7-18.
[13]
Herman-Antosiewicz A, Johnson DE, Singh SV. Sulforaphane causes autophagy to inhibit release of cytochrome C and apoptosis in human prostate cancer cells[J]. Cancer Res, 2006, 66(11): 5828-5835.
[14]
Cheng J, Wei HL, Chen J, et al. Antitumor effect of arsenic trioxide in human K562 and K562/ADM cells by autophagy[J]. Toxicol Mech Methods, 2012, 22(7): 512-519.
[15]
魏清,万小云. 自噬的诱导机制及其在肿瘤治疗中的作用[J]. 国际病理科学与临床杂志,2008, 28(1): 45-48.
[16]
Liang XH, Jackson S, Seaman M, et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1[J]. Nature, 1999, 402(6762): 672-676.
[17]
Pattingre S, Espert L, Biard-Piechaczyk M, et al. Regulation of macroautophagy by mTOR and Beclin 1 complexes[J]. Biochimie, 2008, 90(2): 313-323.
[18]
Liang XH, Kleeman LK, Jiang HH, et al. Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein[J]. J Virol, 1998, 72(11): 8586-8596.
[19]
Erlich S, Mizrachy L, Segev O, et al. Differential interactions between Beclin 1 and Bcl-2 family members[J]. Autophagy, 2007, 3(6): 561-568.
[20]
Chipuk JE, Moldoveanu T, Llambi F, et al. The BCL-2 family reunion[J]. Mol Cell, 2010, 37(3): 299-310.
[21]
Wirawan E, Vande Walle L, Kersse K, et al. Caspase-mediated cleavage of Beclin-1 inactivates Beclin-1-induced autophagy and enhances apoptosis by promoting the release of proapoptotic factors from mitochondria[J]. Cell Death Dis, 2010, 1: e18.
[22]
Li X, Su J, Xia M, et al. Caspase-mediated cleavage of Beclin1 inhibits autophagy and promotes apoptosis induced by S1 in human ovarian cancer SKOV3 cells[J]. Apoptosis, 2016, 21(2): 225-238.
[23]
Shin JY, Hong SH, Kang B, et al. Overexpression of Beclin1 induced autophagy and apoptosis in lungs of K-rasLA1 mice[J]. Lung Cancer, 2013, 81(3): 362-370.
[24]
Adams J. The development of proteasome inhibitors as anticancer drugs[J]. Cancer Cell, 2004, 5(5): 417-421.
[25]
Kisselev AF, Goldberg AL.Proteasome inhibitors: from research tools to drug candidates[J]. Chem Biol, 2001, 8(8):739-758.
[26]
Zhu H, Zhang L, Dong F, et al. Bik/NBK accumulation correlates with apoptosis-induction by bortezomib (PS-341, Velcade) and other proteasome inhibitors[J]. Oncogene, 2005, 24(31): 4993-4999.
[27]
Ding WX, Ni HM, Chen X, et al. A coordinated action of Bax, PUMA, and p53 promotes MG132-induced mitochondria activation and apoptosis in colon cancer cells[J]. Mol Cancer Ther, 2007, 6(3): 1062-1069.
[28]
Pigneux A, Mahon FX, Moreau-Gaudry F, et al. Proteasome inhibition specifically sensitizes leukemic cells to anthracyclin-induced apoptosis through the accumulation of Bim and Bax pro-apoptotic proteins[J]. Cancer Biol Ther, 2007, 6(4): 603-611.
[29]
何洁儿,刘良平,詹姣,等. 抑制泛素-蛋白酶体途径对晶状体上皮细胞自噬的诱导作用[J]. 广东医学,2014, 35(1): 56-58.
[30]
Liu D, Gao M, Yang Y, et al. Inhibition of autophagy promotes cell apoptosis induced by the proteasome inhibitor MG-132 in human esophageal squamous cell carcinoma EC9706 cells[J]. Oncol Lett, 2015, 9(5): 2278-2282.
[31]
张静,李伟,章康健,等. MG132抑制肝癌细胞Bel-7404生长的机制研究[J]. 生物化学与生物物理进展,2010, 37(6): 627-634.
[32]
French LE, Tschopp J. Protein-based therapeutic approaches targeting death receptors[J]. Cell Death Differ, 2003, 10(1): 117-123.
[33]
Chen JJ, Bozza WP, Di X, et al. H-Ras regulation of TRAIL death receptor mediated apoptosis[J]. Oncotarget, 2014, 5(13): 5125-5137.
[34]
Saulle E, Petronelli A, Pasquini L, et al. Proteasome inhibitors sensitize ovarian cancer cells to TRAIL induced apoptosis[J]. Apoptosis, 2007, 12(4): 635-655.
[35]
Han J, Back SH, Hur J, et al. ER-stress-induced transcriptional regulation increases protein synthesis leading to cell death[J]. Nat Cell Biol, 2013, 15(5): 481-490.
[36]
Oyadomari S, Mori M. Roles of CHOP/GADD153 in endoplasmic reticulum stress[J]. Cell Death Differ, 2004, 11(4): 381-389.
[37]
Li Y, Guo Y, Tang J, et al. New insights into the roles of CHOP-induced apoptosis in ER stress[J]. Acta Biochim Biophys Sin (Shanghai), 2014, 46(8): 629-640.
[38]
麻庆乐,卢德赵. 葡萄糖调节蛋白78的研究进展[J]. 生命科学,2017, 29(4): 331-335.
[39]
唐隽,刘川,都伟,等. GRP78在蛋白酶体抑制剂诱导卵巢癌细胞凋亡中的作用[J]. 中国计划生育学杂志,2015, 23(11): 739-742.
[40]
唐隽,刘川,都伟. 蛋白酶体抑制剂通过内质网应激途径诱导卵巢癌细胞凋亡的研究[J]. 中国计划生育学杂志,2015, 23(8): 520-523, 529.
[41]
Du ZX, Meng X, Zhang HY, et al. Caspase-dependent cleavage of BAG3 in proteasome inhibitors-induced apoptosis in thyroid cancer cells[J]. Biochem Biophys Res Commun, 2008, 369(3): 894-898.
[42]
Doong H, Vrailas A, Kohn EC. What′s in the ′BAG′:a functional domain analysis of the BAG-family proteins[J]. Cancer Lett, 2002, 188(1-2): 25-32.
[43]
Wang HQ, Meng X, Gao YY, et al. Characterization of BAG3 cleavage during apoptosis of pancreatic cancer cells[J]. J Cell Physiol, 2010, 224(1): 94-100.
[44]
穆庆,李百鸥. 蛋白酶体抑制剂诱导卵巢癌SKOV3细胞凋亡中伴随caspase依赖的BAG3剪切[J]. 现代肿瘤医学,2013, 21(5): 991-994.
[45]
Pahl HL. Activators and target genes of Rel/NF-kappaB transcription factors[J]. Oncogene, 1999, 18(49): 6853-6866.
[46]
Chen FE, Ghosh G. Regulation of DNA binding by Rel/NF-kappaB transcription factors: structural views[J]. Oncogene, 1999, 18(49): 6845-6852.
[47]
Barkett M, Gilmore TD. Control of apoptosis by Rel/NF-kappaB transcription factors[J]. Oncogene, 1999, 18(49): 6910-6924.
[48]
Wang CY, Mayo MW, Korneluk RG, et al. NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation[J]. Science, 1998, 281(5383): 1680-1683.
[49]
Guttridge DC, Albanese C, Reuther JY, et al. NF-kappaB controls cell growth and differentiation through transcriptional regulation of cyclin D1[J]. Mol Cell Biol, 1999, 19(8): 5785-5799.
[50]
马忠平,顾光华,贾玉芳. 蛋白酶体抑制剂MG132对Caov-3细胞中NF-κB、CycLinD1表达的影响[J]. 实用临床医药杂志,2011, 15(17): 46-48.
[51]
顾光华,张磊,李彩霞. MG132、顺铂联合用药对Caov-3细胞中NF-κB、VEGF表达的影响[J]. 实用临床医药杂志,2010, 14(17): 22-25.
[52]
Liu C, Yan X, Wang HQ, et al. Autophagy-independent enhancing effects of Beclin 1 on cytotoxicity of ovarian cancer cells mediated by proteasome inhibitors[J]. BMC Cancer, 2012, 12(1): 622.
[53]
刘川,王华芹,高雁艳,等. 3-甲基腺嘌呤对蛋白酶体抑制剂MG132抗卵巢癌A2870细胞作用的影响[J]. 现代肿瘤医学,2013, 21(4): 682-685.
[54]
刘川,王华芹,高雁艳,等. 蛋白酶体抑制剂诱导OVCAR3卵巢癌细胞自噬的机制研究[J]. 现代肿瘤医学,2013, 21(8): 1680-1684.
[55]
郭娜,彭芝兰. 蛋白酶体抑制剂MG132诱导卵巢癌SKOV3细胞凋亡和自噬的作用机制[J]. 国际妇产科学杂志,2017, 44(1): 44-47, 94, 123.
[56]
Guo N, Peng Z, Zhang J. Proteasome inhibitor MG132 enhances sensitivity to cisplatin on ovarian carcinoma cells in vitro and in vivo[J]. Int J Gynecol Cancer, 2016, 26(5): 839-844.
[1] 卢菊, 赵胜, 范建华, 高艳多. 探讨IOTA、GI-RADS及O-RADS在附件肿瘤良恶性鉴别诊断中的价值[J/OL]. 中华医学超声杂志(电子版), 2024, 21(05): 484-490.
[2] 吴杰, 周志强, 符菁, 李喜功, 张钦. 吸入性氢气对大鼠脊髓损伤后自噬及神经功能的影响[J/OL]. 中华危重症医学杂志(电子版), 2024, 17(05): 363-371.
[3] 张舒沁, 陈练. 产后宫腔内妊娠物残留的诊断和临床处理[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(05): 493-497.
[4] 钟雅雯, 王煜, 王海臻, 黄莉萍. 肌苷通过抑制线粒体通透性转换孔开放缓解缺氧/复氧诱导的人绒毛膜滋养层细胞凋亡[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(05): 525-533.
[5] 石皆春, 范子玉, 邢燕. 不同筛查方法预警宫颈原位腺癌的效能[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(05): 575-581.
[6] 唐丹, 姚晓曦, 杨博文, 薛绍龙, 李梦瑶, 韦柳杏, 郄明蓉. 双肾上腺皮质激素样激酶1对子宫内膜样腺癌患者临床特征的影响[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(05): 582-590.
[7] 魏艺, 周羽西, 杨烨, 凌秀凤, 赵纯. 微小RNA对子宫内膜容受性影响的研究现状[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(03): 266-270.
[8] 李争光, 宰爽嘉, 吴火峰, 孙华, 张永博, 陈浏阳, 戴睿, 张亮. 昼夜节律相关因子在椎间盘退行性变发病机制中作用的研究进展[J/OL]. 中华损伤与修复杂志(电子版), 2024, 19(05): 457-461.
[9] 孙鸿坤, 艾虹, 陈正. 内质网应激介导的牙周炎骨改建失衡的研究进展[J/OL]. 中华口腔医学研究杂志(电子版), 2024, 18(04): 211-218.
[10] 郑俊, 吴杰英, 谭海波, 郑安全, 李腾成. EGFR-MEK-TZ三联合分子的构建及其对去势抵抗性前列腺癌细胞增殖与凋亡的影响[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(05): 503-508.
[11] 黄程鑫, 陈莉, 刘伊楚, 王水良, 赖晓凤. OPA1 在乳腺癌组织的表达特征及在ER阳性乳腺癌细胞中的生物学功能研究[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(05): 275-284.
[12] 季加翠, 孙春斌, 罗恩丽. 姜黄素通过调节NF-κB/NLRP3通路减轻LPS诱导小胶质细胞神经炎症损伤[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(04): 193-203.
[13] 杜霞, 马梦青, 曹长春. 造影剂诱导的急性肾损伤的发病机制及干预靶点研究进展[J/OL]. 中华肾病研究电子杂志, 2024, 13(05): 279-282.
[14] 史清泉, 苗彬, 王烁, 陶琳, 沈晨. miR-181a-5p 靶向ATG5 抑制雨蛙素诱导的大鼠胰腺腺泡细胞AR42J自噬的机制研究[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 524-530.
[15] 刘霖, 张文欢, 宋雅茹, 姜云璐. Apelin-13 在阿尔茨海默病中的神经保护作用机制研究进展[J/OL]. 中华诊断学电子杂志, 2024, 12(04): 276-280.
阅读次数
全文


摘要


AI


AI小编
你好!我是《中华医学电子期刊资源库》AI小编,有什么可以帮您的吗?