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聚腺苷二磷酸核糖聚合酶[poly(adenosine diphosphate-ribose)polymerases,PARP]是一种能够催化二磷酸腺苷(adenosine diphosphate,ADP)核糖向靶蛋白转移的酶家族。PARP-1作为一种重要因子参与到DNA损伤修复过程中,促进DNA修复,恢复肿瘤细胞的增殖。因此,靶向抑制PARP-1协同DNA损伤剂成为一种极具潜力的治疗策略。我们对PARP-1作为肿瘤细胞放射增敏靶点的研究进展进行简单综述。
靶向PARP-1调控肿瘤细胞放射敏感性的研究进展
Research progress of targeting PARP-1 to regulate radiosensitivity of tumor cells
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摘要: 放疗是晚期肿瘤的主要治疗手段,然而,由于肿瘤耐受和抵抗的出现,其治疗效果不佳。因此,纠正肿瘤放疗抵抗或提高其放疗敏感性成为迫切需要解决的问题。聚腺苷二磷酸核糖聚合酶(PARP)1是一种功能丰富的核蛋白,鉴于其在染色质结构调节和DNA损伤修复等细胞过程中的重要作用,PARP-1被认为是最具有潜力的一种放射增敏靶点。笔者就靶向PARP-1调控肿瘤细胞放射敏感性的研究进展作一综述。
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关键词:
- 辐射增敏药 /
- 聚ADP核糖聚合酶类 /
- 肿瘤
Abstract: Radiotherapy is the main treatment for advanced tumor. However, due to the emergence of tumor tolerance and resistance, the treatment effect is not ideal. Therefore, it is urgent to correct the resistance or improve the sensitivity of radiotherapy. Poly (adenosine diphosphate-ribose) polymerase (PARP)1 is a member of a functionally rich nuclear protein. In view of its important role in cellular processes such as regulation of chromatin structure and repair of DNA damage, PARP-1 is considered to be the most potential target for radiosensitization. In this paper, the author reviews the research progress of targeting PARP-1 to regulate radiosensitization of tumor cells.-
Key words:
- Radiation-sensitizing agents /
- Poly(ADP-ribose) polymerases /
- Neoplasms
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[1] Singh SS, Sarma JARP, Narasu L, et al. A review on PARP1 inhibitors: pharmacophore modeling, virtual and biological screening studies to identify novel PARP1 inhibitors[J]. Curr Top Med Chem, 2014, 14(17): 2020−2030. DOI: 10.2174/1568026614666140929152123. [2] Alemasova EE, Lavrik OI. Poly(ADP-ribosyl)ation by PARP1: reaction mechanism and regulatory proteins[J]. Nucleic Acids Res, 2019, 47(8): 3811−3827. DOI: 10.1093/nar/gkz120. [3] Rajawat J, Shukla N, Mishra DP. Therapeutic targeting of poly(ADP-Ribose) polymerase-1(PARP1) in cancer: current developments, therapeutic strategies, and future opportunities[J]. Med Res Rev, 2017, 37(6): 1461−1491. DOI: 10.1002/med.21442. [4] Engbrecht M, Mangerich A. The nucleolus and PARP1 in cancer biology[J]. Cancers (Basel), 2020, 12(7): 1813. DOI: 10.3390/cancers12071813. [5] Ciccarone F, Zampieri M, Caiafa P. PARP1 orchestrates epigenetic events setting up chromatin domains[J]. Semin Cell Dev Biol, 2017, 63: 123−134. DOI: 10.1016/j.semcdb.2016.11.010. [6] Keung MYT, Wu YY, Vadgama JV. PARP inhibitors as a therapeutic agent for homologous recombination deficiency in breast cancers[J]. J Clin Med, 2019, 8(4): 435. DOI: 10.3390/jcm8040435. [7] Chaudhuri AR, Nussenzweig A. The multifaceted roles of PARP1 in DNA repair and chromatin remodelling[J]. Nat Rev Mol Cell Biol, 2017, 18(10): 610−621. DOI: 10.1038/nrm.2017.53. [8] Pascal JM. The comings and goings of PARP-1 in response to DNA damage[J]. DNA Repair(Amst), 2018, 71: 177−182. DOI: 10.1016/j.dnarep.2018.08.022. [9] Bryant HE, Schultz N, Thomas HD, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase[J]. Nature, 2005, 434(7035): 913−917. DOI: 10.1038/nature03443. [10] Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy[J]. Nature, 2005, 434(7035): 917−921. DOI: 10.1038/nature03445. [11] Majuelos-Melguizo J, Rodríguez MI, López-Jiménez L, et al. PARP targeting counteracts gliomagenesis through induction of mitotic catastrophe and aggravation of deficiency in homologous recombination in PTEN-mutant glioma[J/OL]. Oncotarget, 2015, 6(7): 4790−4803[2019-10-18]. https://www.oncotarget.com/article/2993/text. DOI: 10.18632/oncotarget.2993. [12] Ahel D, Horejsi Z, Wiechens N, et al. Poly(ADP-ribose)-dependent regulation of DNA repair by the chromatin remodeling enzyme ALC1[J]. Science, 2009, 325(5945): 1240−1243. DOI: 10.1126/science.1177321. [13] Engbrecht M, Mangerich A. The nucleolus and PARP1 in cancer biology[J/OL]. Cancers(Basel), 2020, 12(7): 1813[2019-10-18]. https://www.mdpi.com/2072-6694/12/7/1813. DOI: 10.3390/cancers12071813. [14] Pommier Y, O'Connor MJ, de Bono J. Laying a trap to kill cancer cells: PARP inhibitors and their mechanisms ofaction[J]. Sci Transl Med, 2016, 8(362): 362ps17[2019-10-18]. https://stm.sciencemag.org/content/8/362/362ps17.short. DOI: 10.1126/scitranslmed.aaf9246. [15] Veuger SJ, Curtin NJ, Richardson CJ, et al. Radiosensitization and DNA repair inhibition by the combined use of novel inhibitors of DNA-dependent protein kinase and Poly(ADP-ribose) polymerase-1[J]. Cancer Res, 2003, 63(18): 6008−6015. [16] Powell C, Mikropoulos C, Kaye SB, et al. Pre-clinical and clinical evaluation of PARP inhibitors as tumour-specific radiosensitisers[J]. Cancer Treat Rev, 2010, 36(7): 566−575. DOI: 10.1016/j.ctrv.2010.03.003. [17] Jain PG, Patel BD. Medicinal chemistry approaches of poly ADP-ribose polymerase 1 (PARP1) inhibitors as anticancer agents—A recent update[J]. Eur J Med Chem, 2019, 165: 198−215. DOI: 10.1016/j.ejmech.2019.01.024. [18] Löser DA, Shibata A, Shibata AK, et al. Sensitization to radiation and alkylating agents by inhibitors of Poly(ADP-ribose) polymerase is enhanced in cells deficient in DNA double-strand break repair[J]. Mol Cancer Ther, 2010, 9(6): 1775−1787. DOI: 10.1158/1535-7163.MCT-09-1027. [19] Bridges KA, Toniatti C, Buser CA, et al. Niraparib (MK-4827), a novel poly(ADP-ribose) polymerase inhibitor, radiosensitizes human lung and breast cancer cells[J/OL]. Oncotarget, 2014, 5(13): 5076−5086[2019-10-18]. https://www.oncotarget.com/article/2083/text. DOI: 10.18632/oncotarget.2083. [20] Liu C, Gross N, Li YS, et al. PARP inhibitor olaparib increases the sensitization to radiotherapy in FaDu cells[J]. J Cell Mod MeD, 2020, 24(4): 2444−2450. DOI: 10.1111/jcmm.14929. [21] Oei AL, Ahire VR, van Leeuwen CM, et al. Enhancing radiosensitisation of BRCA2-proficient and BRCA2-deficient cell lines with hyperthermia and PARP1-i[J]. Int J Hyperthermia, 2018, 34(1): 39−48. DOI: 10.1080/02656736.2017.1324642. [22] Dungey FA, Löser DA, Chalmers AJ. Replication-dependent radiosensitization of human glioma cells by inhibition of poly(ADP-ribose) polymerase: mechanisms and therapeutic potential[J]. Int J Radiat Oncol Biology Phys, 2008, 72(4): 1188−1197. DOI: 10.1016/j.ijrobp.2008.07.031. [23] Godon C, Cordelières FP, Biard D, et al. PARP inhibition versus PARP-1 silencing: different outcomes in terms of single-strand break repair and radiation susceptibility[J]. Nucleic Acids Res, 2008, 36(13): 4454−4464. DOI: 10.1093/nar/gkn403. [24] Kötter A, Cornils K, Borgmann K, et al. Inhibition of PARP1-dependent end-joining contributes to olaparib-mediated radiosensitization in tumor cells[J]. Mol Oncol, 2014, 8(8): 1616−1625. DOI: 10.1016/j.molonc.2014.06.008. [25] Mansour WY, Borgmann K, Petersen C, et al. The absence of Ku but not defects in classical non-homologous end-joining is required to trigger PARP1-dependent end-joining[J]. DNA Repair(Amst), 2013, 12(12): 1134−1142. DOI: 10.1016/j.dnarep.2013.10.005. [26] Oing C, Tennstedt P, Simon R, et al. BCL2-overexpressing prostate cancer cells rely on PARP1-dependent end-joining and are sensitive to combined PARP inhibitor and radiation therapy[J]. Cancer Lett, 2018, 423: 60−70. DOI: 10.1016/j.canlet.2018.03.007. [27] Barreto-Andrade JC, Efimova EV, Mauceri HJ, et al. Response of human prostate cancer cells and tumors to combining PARP inhibition with ionizing radiation[J]. Mol Cancer Ther, 2011, 10(7): 1185−1193. DOI: 10.1158/1535-7163.MCT-11-0061. [28] Alotaibi M, Sharma K, Saleh T, et al. Radiosensitization by PARP inhibition in DNA repair proficient and deficient tumor cells: proliferative recovery in senescent cells[J]. Radiat Res, 2016, 185(3): 229−245. DOI: 10.1667/RR14202.1. [29] Mangoni M, Sottili M, Salvatore G, et al. Enhancement of soft tissue sarcoma cell radiosensitivity by poly(ADP-ribose) polymerase-1 inhibitors[J]. Radiat Res, 2018, 190(5): 464−472. DOI: 10.1667/RR15035.1. [30] Li S, Cui ZL, Meng XF. Knockdown of PARP-1 inhibits proliferation and ERK signals, increasing drug sensitivity in osteosarcoma U2OS cells[J]. Oncol Res, 2016, 24(4): 279−286. DOI: 10.3727/096504016X14666990347554. [31] Vance S, Liu E, Zhao LL, et al. Selective radiosensitization of p53 mutant pancreatic cancer cells by combined inhibition of Chk1 and PARP1[J]. Cell Cycle, 2011, 10(24): 4321−4329. DOI: 10.4161/cc.10.24.18661. [32] Karnak D, Engelke CG, Parsels LA, et al. Combined inhibition of Wee1 and PARP1/2 for radiosensitization in pancreatic cancer[J]. Clin Cancer Res, 2014, 20(19): 5085−5096. DOI: 10.1158/1078-0432.ccr-14-1038. [33] Azad A, Bukczynska P, Jackson S, et al. Co-targeting deoxyribonucleic acid–dependent protein kinase and poly(adenosine diphosphate-ribose) polymerase-1 promotes accelerated senescence of irradiated cancer cells[J]. Int J Radiat Oncol Biol Phys, 2014, 88(2): 385−394. DOI: 10.1016/j.ijrobp.2013.10.043. [34] Zhou ZR, Zhu XD, Zhao W, et al. Poly(ADP-ribose) polymerase-1 regulates the mechanism of irradiation-induced CNE-2 human nasopharyngeal carcinoma cell autophagy and inhibition of autophagy contributes to the radiation sensitization of CNE-2 cells[J]. Oncol Rep, 2013, 29(6): 2498−2506. DOI: 10.3892/or.2013.2382. [35] Chen ZT, Zhao W, Qu S, et al. PARP-1 promotes autophagy via the AMPK/mTOR pathway in CNE-2 human nasopharyngeal carcinoma cells following ionizing radiation, while inhibition of autophagy contributes to the radiation sensitization of CNE-2 cells[J]. Mol Med Rep, 2015, 12(2): 1868−1876. DOI: 10.3892/mmr.2015.3604. [36] 王维, 段碧霞, 曾丽. PARP抑制剂对Lewis肺癌细胞及移植瘤放疗增敏作用及其机制[J]. 中国肺癌杂志, 2016, 19(1): 16−23. DOI: 10.3779/j.issn.1009-3419.2016.01.02.
Wang W, Duan BX, Zeng L. Effect and mechanism of radiosensitization of poly (ADP-ribose) polymerase inhibitor on lewis cells and xenografts[J]. Chin J Lung Cancer, 2016, 19(1): 16−23. DOI: 10.3779/j.issn.1009-3419.2016.01.02.[37] 杨莹, 王静, 陆晓媛. PARP抑制剂veliparib对Ishikawa子宫内膜癌细胞放疗增敏作用[J]. 徐州医科大学学报, 2018, 38(2): 101−105. DOI: 10.3969/j.issn.1000-2065.2018.02.008.
Yang Y, Wang J, Lu XY. The radiosensitization effect of veliparib, a PARP inhibitor, on Ishikawa endometrial cancer cells[J]. Acta Academiae Medicine XuZhou, 2018, 38(2): 101−105. DOI: 10.3969/j.issn.1000-2065.2018.02.008.[38] Liu Q, Gheorghiu L, Drumm M, et al. PARP-1 inhibition with or without ionizing radiation confers reactive oxygen species-mediated cytotoxicity preferentially to cancer cells with mutant TP53[J]. Oncogene, 2018, 37(21): 2793−2805. DOI: 10.1038/s41388-018-0130-6. [39] Mao YZ, Huang X, Shuang ZY, et al. PARP inhibitor olaparib sensitizes cholangiocarcinoma cells to radiation[J]. Cancer Med, 2018, 7(4): 1285−1296. DOI: 10.1002/cam4.1318.
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