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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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β-lapachone：一种在胰腺癌中具有独特NQO1特异性凋亡的有前景的抗癌药物

卷 22, 期 7, 2022

发表于: 31 May, 2022

页: [537 - 540] 页: 4

弟呕挨: 10.2174/1568009622666220427121127

摘要

癌症是全世界的主要健康问题之一，需要更有效的药物用于临床。最近正在研究的一种可能的化疗药物是β-lapachone。β-lapachone（1,2-萘醌）对显示烟酰胺二磷酸醌氧化还原酶-1（NQO1）水平升高的肿瘤具有很好的活性。发现NQO1在胰腺肿瘤细胞中上调，因此β-lapachone可在胰腺肿瘤等各种癌症中产生细胞毒性。β-lapachone在琼脂中具有独立生长和克隆形成细胞存活。使用NAD（P）H醌氧化还原酶-1抑制剂双香酚可以阻止β-lapachone的细胞杀伤作用。在先前建立的小鼠胰腺癌异种移植物中，β-lapachone在口服时抑制肿瘤生长，而不是与环糊精联合使用，以提高其生物利用度。

关键词: NAD（P）H醌氧化还原酶-1，β-lapachone，活性氧物种，醌，环糊精，人胰腺癌。

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图形摘要

[1]
Gomes, C.L.; de Albuquerque Wanderley Sales, V.; Gomes de Melo, C.; Ferreira da Silva, R.M.; Vicente Nishimura, R.H.; Rolim, L.A.; Rolim Neto, P.J. Beta-lapachone: Natural occurrence, physicochemical properties, biological activities, toxicity and synthesis. Phytochemistry, 2021, 186, 112713.
[http://dx.doi.org/10.1016/j.phytochem.2021.112713] [PMID: 33667813]
[2]
Beg, M.S.; Huang, X.; Silvers, M.A.; Gerber, D.E.; Bolluyt, J.; Sarode, V.; Fattah, F.; Deberardinis, R.J.; Merritt, M.E.; Xie, X.J.; Leff, R.; Laheru, D.; Boothman, D.A. Using a novel NQO1 bioactivatable drug, beta-lapachone (ARQ761), to enhance chemotherapeutic effects by metabolic modulation in pancreatic cancer. J. Surg. Oncol., 2017, 116(1), 83-88.
[http://dx.doi.org/10.1002/jso.24624] [PMID: 28346693]
[3]
Yang, Y.P.; Qi, F.J.; Qian, Y.P.; Bao, X.Z.; Zhang, H.C.; Ma, B.; Dai, F.; Zhang, S.X.; Zhou, B. Developing push-pull hydroxylphenylpolyenylpyridinium chromophores as ratiometric two-photon fluorescent probes for cellular and intravital imaging of mitochondrial NQO1. Anal. Chem., 2021, 93(4), 2385-2393.
[http://dx.doi.org/10.1021/acs.analchem.0c04279] [PMID: 33439630]
[4]
Chen, Y.; Liu, Y.; Chen, C.; Lv, J.; Zhang, J.; Li, G. An electrochemical method to assay the activity of NAD (P) H: Quinone oxidoreductase 1. Sens. Actuators B Chem., 2015, 216, 343-348.
[http://dx.doi.org/10.1016/j.snb.2015.04.059]
[5]
Zhang, Y.; Knatko, E.V.; Higgins, M.; Dayalan Naidu, S.; Smith, G.; Honda, T.; de la Vega, L.; Dinkova-Kostova, A.T. Pirin, an Nrf2-regulated protein, is overexpressed in human colorectal tumors. Antioxidants, 2022, 11(2), 262.
[http://dx.doi.org/10.3390/antiox11020262] [PMID: 35204145]
[6]
Ross, D.; Siegel, D. The diverse functionality of NQO1 and its roles in redox control. Redox Biol., 2021, 41, 101950.
[http://dx.doi.org/10.1016/j.redox.2021.101950] [PMID: 33774477]
[7]
Zhang, Y.; Zhang, G.; Zeng, Z.; Pu, K. Activatable molecular probes for fluorescence-guided surgery, endoscopy and tissue biopsy. Chem. Soc. Rev., 2022, 51, 566-593.
[http://dx.doi.org/10.1039/D1CS00525A]
[8]
Zhang, L. Chen, Z.; Yang, K.; Liu, C.; Gao, J.; Qian, F. β-Lapachone and paclitaxel combination micelles with improved drug encapsulation and therapeutic synergy as novel nanotherapeutics for NQO1-targeted cancer therapy. Mol. Pharm., 2015, 12(11), 3999-4010.
[http://dx.doi.org/10.1021/acs.molpharmaceut.5b00448] [PMID: 26415823]
[9]
Ke, L.I.A.O.; Fang, N.I.U.; Hai-Ping, H.A.O.; Guang-Ji, W.A.N.G. Advances on structure-activity relationship of NQO1-targeting antitumor quinones. Chin. J. Nat. Med., 2012, 10(3), 170-176.
[http://dx.doi.org/10.3724/SP.J.1009.2012.00170]
[10]
Silvers, M.A.; Deja, S.; Singh, N.; Egnatchik, R.A.; Sudderth, J.; Luo, X.; Beg, M.S.; Burgess, S.C.; DeBerardinis, R.J.; Boothman, D.A.; Merritt, M.E. The NQO1 bioactivatable drug, β-lapachone, alters the redox state of NQO1+ pancreatic cancer cells, causing perturbation in central carbon metabolism. J. Biol. Chem., 2017, 292(44), 18203-18216.
[http://dx.doi.org/10.1074/jbc.M117.813923] [PMID: 28916726]
[11]
Moore, Z.; Chakrabarti, G.; Lyssiotis, C.; Deberardinis, R.; David, B.A. Abstract B47: Modulating the NQO1-dependent ‘kiss of death’mechanism of action of NQO1 bioactivatable drugs. 2015, 2015, B47.
[12]
Peng, K.; Liang, B.B.; Liu, W.; Mao, Z.W. What blocks more anticancer platinum complexes from experiment to clinic: Major problems and potential strategies from drug design perspectives. Coord. Chem. Rev., 2021, 449, 214210.
[http://dx.doi.org/10.1016/j.ccr.2021.214210]
[13]
Mahar, R.; Chang, M.C.; Merritt, M.E. Measuring NQO1 Bioactivation Using [2H7]Glucose. Cancers (Basel), 2021, 13(16), 4165.
[http://dx.doi.org/10.3390/cancers13164165] [PMID: 34439319]

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