中华临床医师杂志(电子版) 2017年2月,11卷4期

综 述

细胞凋亡抑制蛋白-1在宫颈癌及宫颈癌化疗耐药方面的研究进展

高艳梅 魏芳

030001 太原,山西医科大学第二医院妇产科
魏芳,Email: 2yuanweifang@163.com

摘要:细胞凋亡抑制蛋白-1(c-IAP1)属于凋亡抑制蛋白家族(IAPs),是一种重要的细胞内凋亡调节蛋白,通过抑制caspase酶活性以及参与调节核转录因子κB(NF-κB)信号通路抑制细胞凋亡并促进细胞存活,进而参与肿瘤形成及化疗耐药,亦可通过调节Rho家族(Ras homologue)中Ras相关的C3肉毒素底物1(Rac1)等的活性,在肿瘤的转移中发挥重要作用。研究表明,c-IAP1在宫颈癌的发生发展、治疗及预后判断方面均发挥重要作用,现就其在宫颈癌及宫颈癌化疗耐药方面的研究进展作一简要概述。

关键词:细胞凋亡抑制蛋白-1; 宫颈肿瘤; 人乳头瘤病毒; 宫颈癌化疗耐药

Research progress of c-IAP1 in cervical cancer and chemotherapy resistance

Gao Yanmei, Wei Fang.

Department of Gynecology and Obstetrics, the Second Hospital of Shanxi Medical University, Taiyuan 030001, China
Wei Fang, Email: 2yuanweifang@163.com

Abstract:Cellular inhibitor of apoptosis protein 1 (c-IAP1), a member of apoptosis inhibitory protein family, is an important intracellular apoptosis regulatory protein, which inhibits apoptosis and promotes cell survival by inhibiting the activity of caspase and participating in the regulation of NF-κB signaling pathway, and then participates in the formation of tumor and chemotherapy drug resistance, it can also play an important role in the metastasis of tumors by regulating the activity of Rac1 in the Rho family. Studies have indicated that c-IAP1 plays an important role in the occurrence, development, treatment and prognosis of cervical cancer, this paper gave a brief overview of their progress on cervical cancer and resistance to chemotherapy in cervical cancer.

Keywords:Cellular apoptosis inhibitory protein 1; Uterine cervical neoplasms; Human papilloma virus; Resistant to chemotherapy in cervical cancer

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参考文献

  [1] Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2015[J]. CA Cancer J Clin, 2015, 65: 5-29.

  [2] Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012[J]. CA Cancer J Clin, 2015, 65: 87-108.

  [3] Czabotar P E, Lessene G, Starsser A, et al. Control of apoptosis by the Bcl-2 protein family: implications for physiology and therapy[J]. Nat Rev Mol Cell Biol, 2014, 15(1): 49-63.

  [4] Kulathila R, Vash B, Sage D, et al. The structure of the BIR3 domain of cIAP1 in complex with the N-terminal peptides of SMAC and easpase-9[J]. Acta Crystallogr D Biol Crystallogr, 2009, 65(1): 58-66.

  [5] Vince JE, Pantaki D, Feltham R, et al. TRAF2 must bind to cellular inhibitors of apoptosis for tumor necrosis factor(TNF) To efficiently activate NF-κB and to prevent TNF-induced apoptosis[J]. J Biol Chem, 2009, 284(51): 35906-35915.

  [6] Roy J, Pallepati P, Bettaieb A, et al. Acrolein induces a cellular stress response and triggers mitochondrial apoptosis in A549 cells[J]. Chem Biol Interact, 2009, 181(2): 154-167.

  [7] Kempkensteffen C, Hinz S, Christoph F, et al. Expression parameters of the inhibitors of apoptosis cIAP1 and cIAP2 in renal cell carcinomas and their prognostic relevance[J]. Int J Cancer, 2007, 120: 1081-1086.

  [8] Gyrd-Hansen M, Meier P. IAPs: From caspase inhibitors to modulators of NF-kappaB, inflammation and cancer[J]. Nat Rev Cancer, 2010, 10: 561-574.

  [9] Silke J, Brink R. Regulation of TNFRSF and innate immune signalling complexes by TRAFs and cIAPs[J]. Cell Death Differ, 2010, 17: 35-45.

  [10] Mehrotra S, Languino LR, Raskett CM, et al. IAP regulation of metastasis[J]. Cancer Cell, 2010, 17(1): 53-64.

  [11] Kamai T, Arai K, Sumi S, et al. The rho/rho kinase pathway is involved in the progression of testiculargerm cell tumour[J]. BJU Int, 2002, 89(4): 449-453.

  [12] Tripat KO, Taner D, Jennifer CH, et al. IAPs regulate the plasticity of cell migration by directly targeting Rac1 for degradation[J]. EMBO J, 2012, 31(1): 14-28.

  [13] Srinivasula SM, Ashwell JD. IAPs: what's inaname?[J]. Mol Cell, 2008, 30: 123-135.

  [14] Zender L, Spector MS, Xue W, et al. Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach[J]. Cell, 2006, 125: 1253-1267.

  [15] Xu L, Zhu J, Hu X, et al. c-IAP1 cooperates with Myc by acting a saubiquitinligase for Mad1[J]. Mol Cell, 2007, 28: 914-922.

  [16] Tamm I, Kornblau SM, Segall H, et al. Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias[J]. Clin Cancer Res, 2000, 6(5): 1796-1803.

  [17] 许杨, 刘芳, 周兰萍, 等. c-IAP1在食管鳞癌中的表达及其对化疗敏感性的影响[J]. 世界华人消化杂志, 2011, 19(11): 1138-1144.

  [18] 李晨星, 刘忠宇, 赵恩锋. 细胞凋亡抑制蛋白cIAP与卵巢癌耐药性的研究进展[J]. 现代生物医学进展, 2012, 12(18): 3584-3585.

  [19] Mitsuishi T, Iwabu Y, Tokunaga K, et al. Combined analysis of cell growth and apoptosis-regulating proteins in HPVs associated anogenital tumors[J]. BMC Cancer, 2010, 27(10): 118.

  [20] Honegger A, Leitz J, Bulkescher J, et al. Silencing of human papillomavirus(HPV) E6/E7 oncogene expression affects both the contents and the amounts of extracellular microvesicles released from HPV-positive cancer cells[J]. Cancer, 2013, 133(7): 1631-1642.

  [21] 朱明玥. 新疆维吾尔族宫颈癌组织中全基因组表达谱分析及与凋亡相关的基因c-IAP1. Bcl-zl, BcI2的检测[D]. 乌鲁木齐: 新疆医科大学, 2014.

  [22] Imoto I, Tsuda H, Hirasawa A, et al. Expression of cIAP1, a target for 11q22 amplification, correlates with resistance of cervical cancers to radiotherapy[J]. Cancer Research, 2002, 62(17): 4860-4866.

  [23] 贾丁玲. c-IAP1、MCM2、P-gp预测宫颈鳞癌新辅助化疗疗效的价值[D]. 太原: 山西医科大学, 2014.

  [24] Benetatos CA, Mitsuuchi Y, Burns JM, et al. Birinapant(TL32711), a bivalent SMAC mimetic, targets TRAF2-associated cIAPs, abrogates TNF-induced NF-κB activation, and is active in patient-derived xenograft models[J]. Mol Cancer Ther, 2014, 13(4): 867-879.

  [25] Ebert G, Allison C, Preston S, et al. Eliminating hepatitis B by antagonizing cellular inhibitors of apoptosis[J]. Proc Natl Acad Sci U S A, 2015, 112(18): 5803-5808.

  [26] Philippos P, Apostolos G, Alexandra V, et al. IAP antagonists Birinapant and AT-406 efficiently synergise with either TRAIL, BRAF, or BCL-2 inhibitors to sensitise BRAFV600E colorectal tumour cells to apoptosis[J]. BMC Cancer, 2016, 16: 624.

  [27] Seigal BA, Connors WH, Fraley A, et al. The discovery of macrocyclic XIAP antagonists from a DNA-programmed chemistry library, and their optimization to give lead compounds with in vivo antitumor activity[J]. J Med Chem, 2015, 58(6): 2855-2861.

  [28] 贺圆圆. c-IAP1在宫颈癌细胞耐药中的作用及其机制[D]. 太原: 山西医科大学, 2015.

(编辑:戚红丹 收稿日期:2016-11-07)