质子泵抑制剂在乳腺癌中的研究进展

doi:10.11904/j.issn.1002-3070.2017.02.017

摘要/Abstract

摘要： 近年一些研究表明,质子泵抑制剂(Proton pump inhibitors,PPIs)不仅在消化系统疾病方面起作用,而且在乳腺癌的治疗中也有重要作用。质子泵抑制剂包括奥美拉唑(Omeprazole)、泮托拉唑(Pantoprazole)、兰索拉唑(Lansoprazole)、埃索美拉唑(Esomeprazole)等,它们通过抑制细胞内质子排出,增加细胞内体pH值等方式,提高乳腺癌化疗药物效果和诱导乳腺癌细胞凋亡。本文就PPIs在乳腺癌中的相关研究加以总结,并讨论PPIs在乳腺癌治疗中的潜在应用。

关键词: 质子泵抑制剂, 乳腺癌, 奥美拉唑, 泮托拉唑

Abstract: In recent years,some studies have been shown that proton pump inhibitors(PPIs)not only play a role in digestive diseases,but it also has an important role in the treatment of breast cancer.PPIs,including omeprazole,pantoprazole,lansoprazole,esomeprazole,etc,improve the effect of breast cancer chemotherapy and induce breast cancer cell apoptosis by inhibiting intracellular proton excretion and increasing intracellular pH.This preview summarizes the study progress of PPIs in breast cancer and the potential application of PPIs in the treatment of breast cancer.

Key words: Proton pump inhibitors, Breast cancer, Omeprazole, Pantoprazole

中图分类号:

R737.9

付应强(综述), 李志高(审校). 质子泵抑制剂在乳腺癌中的研究进展[J]. 实用肿瘤学杂志, 2017, 31(2): 179-182.

FU Yingqiang,LI Zhigao. Research progress of proton pump inhibitors on breast cancer[J]. PRACTICAL ONCOLOGY JOURNAL, 2017, 31(2): 179-182.

参考文献

1 Siegel RL,Miller KD,Jemal A.Cancer statistics,2016[J].Ca A Cancer Journal for Clinicians,2016,66(1):7.
2 Moulder S,Hortobagyi GN.Advances in the treatment of breast cancer[J].Womens Health,2005,1(3):359-363.
3 Zhang S,Wang Y,Li SJ.Lansoprazole induces apoptosis of breast cancer cells through inhibition of intracellular proton extrusion[J].Biochem Biophys Res Commun,2014,448(4):424-429.
4 Wang BY,Zhang J,Wang JL,et al.Intermittent high dose proton pump inhibitor enhances the antitumor effects of chemotherapy in metastatic breast cancer[J].J Exp Clin Cancer Res,2015,34(1):85.
5 Man Y,Lee C,Wang M,et al.Influence of the proton pump inhibitor lansoprazole on distribution and activity of doxorubicin in solid tumors[J].Cancer Sci,2015,106(10):1438-1447.
6 Patel KJ,Lee C,Tan Q,et al.Use of the proton pump inhibitor pantoprazole to modify the distribution and activity of doxorubicin:a potential strategy to improve the therapy of solid tumors[J].Clin Cancer Res,2013,19(24):6766-6776.
7 Goh W,Sleptsova-Freidrich I,Petrovic N.Use of proton pump inhibitors as adjunct treatment for triple-negative breast cancers.An introductory study[J].J Pharm Pharm Sci,2014,17(3):439-446.
8 Jin UH,Lee SO,Pfent C,et al.The aryl hydrocarbon receptor ligand omeprazole inhibits breast cancer cell invasion and metastasis[J].BMC Cancer,2014,14(14):498.
9 刘波,姚鸿萍.临床常用质子泵抑制剂的研究进展[J].西北药学杂志,2014(3):328-330.
10 Shin JM,Kim N.Pharmacokinetics and pharmacodynamics of the proton pump inhibitors[J].J Neurogastroenterol Motil,2013,19(1):25-35.
11 毛煜,佘佳红,袁伯俊.苯并咪唑类质子泵抑制剂的药理和临床研究进展[J].中国新药杂志,2006,15(1):17-21.
12 Rogakou EP,Pilch DR,Orr AH,et al.DNA double-stranded breaks induce histone H2AX hosphorylation on serine 139[J].J Biol Chem,1998,273:5858-5868.
13 Chen YN,Mickley LA,Schwartz AM,et al.Characterization of adriamycin-resistant human breast cancer cells which display overexpression of a novel resistance-related membrane protein[J].J Biol Chem,1990,265:10073-10080.
14 Lee JS,Scala S,Matsumoto Y,et al.Reduced drug accumulation and multidrug resistance in human breast cancer cells without associated P-glycoprotein or MRP overexpression[J].J Cell Biochem,1997,65:513-526.
15 Litman T,Brangi M,Hudson E,et al.The multidrug-resistant phenotype associated with overexpression of the new ABC half-transporter,MXR(ABCG2)[J].J Cell Sci,2000,113:2011-2021.
16 Poland A,Glover E,Kende AS.Stereospecific,high affinity binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin by hepatic cytosol.Evidence that the binding species is receptor for induction of aryl hydrocarbon hydroxylase[J].J Biol Chem,1976,251(16):4936-4946.
17 Dinatale BC,Schroeder JC,Francey LJ,et al.Mechanistic insights into the events that lead to synergistic induction of interleukin 6 transcription upon activation of the aryl hydrocarbon receptor and inflammatory signaling[J].J Biol Chem,2010,285(32):24388-24397.
18 Murray IA,Krishnegowda G,DiNatale BC,et al.Development of a selective modulator of aryl hydrocarbon(Ah)receptor activity that exhibits anti-inflammatory properties[J].Chem Res Toxicol,2010,23(5):955-966.
19 Benson JM,Shepherd DM.Aryl hydrocarbon receptor activation by TCDD reduces inflammation associated with Crohn′s disease[J].Toxicol Sci,2011,120(1):68-78.
20 Murray IA,Morales JL,Flaveny CA,et al.Evidence for ligand-mediated selective modulation of aryl hydrocarbon receptor activity[J].Mol Pharmacol,2010,77(2):247-254.
21 Boitano AE,Cooke MP.Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells[J].Science,2010,329(5997):1345-1348.
22 Quintana FJ,Basso AS,Iglesias AH,et al.Control of T(reg)and T(H)17 cell differentiation by the aryl hydrocarbon receptor[J].Nature,2008,453(7191):65-71.
23 Veldhoen M,Hirota K,Westendorf AM,et al.The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins[J].Nature,2008,453(7191):106-109.
24 Kerkvliet NI,Steppan LB,Vorachek W,et al.Activation of aryl hydrocarbon receptor by TCDD prevents diabetes in NOD mice and increases Foxp3+ T cells in pancreatic lymph nodes[J].Immunotherapy,2009,1(4):539-547.
25 Hsu EL,Yoon D,Choi HH,et al.A proposed mechanism for the protective effect of dioxin against breast cancer[J].Toxicol Sci,2007,98(2):436-444.
26 Hall JM,Barhoover MA,Kazmin D,et al.Activation of the aryl-hydrocarbon receptor inhibits invasive and metastatic features of human breast cancer cells and promotes breast cancer cell differentiation[J].Mol Endocrinol,2010,24(2):359-369.
27 Wang T,Gavin HM,Arlt VM,et al.Aryl hydrocarbon receptor activation during pregnancy,and in adult nulliparous mice,delays the subsequent development of DMBA-induced mammary tumors[J].Int J Cancer,2011,128(7):1509-1523.
28 Di Paolo A,Bocci G.Drug distribution in tumors,mechanisms,role in drug resistance,and methods for modification[J].Curr Oncol Rep,2007,9(2):109-114.
29 Minchinton AI,Tannock IF.Drug penetration in solid tumours[J].Nat Rev,2006,6(8):583-592.
30 Simon S,Roy D,Schindler M.Intracellular pH and the control of multidrug resistance[J].Proc Natl Acad Sci USA,1994,91(3):1128-1132.
31 Tannock IF,Rotin D.Acid pH in tumors and its potential for therapeutic exploitation[J].Cancer Res,1989,49(16):4373-4384.
32 Rotin D,Robinson B,Tannock IF.Influence of hypoxia and an acidic environment on the metabolism and viability of cultured cells:potential implications for cell death in tumors[J].Cancer,1986,46(6):2821-2826.
33 Helmlinger G,Sckell A,Dellian M,et al.Acid production in glycolysis-impaired tumors provides new insights into tumor metabolism[J].Clin Cancer Res,2002,8(4):1284-1291.
34 Gillies RJ,Liu Z,Bhujwalla Z.31P-MRS measurements of extracellular pH of tumors using 3-aminopropylphosphonate[J].Am J Physiol,1994,267(1):195-203.
35 Mccoy CL,Parkins CS,Chaplin DJ,et al.The effect of blood flow modification on intra-and extracellular pH measured by 31P magnetic resonance spectroscopy in murine tumours[J].Br J Cancer,1995,72(4):905-911.
36 Raghunand N,He X,Van SR,et al.Enhancement of chemotherapy by manipulation of tumour pH[J].Br J Cancer,1999,80(7):1005-1011.
37 Liu H,Liu JY,Wu X,et al.Biochemistry,molecular biology,and pharmacology of fatty acid synthase,an emerging therapeutic target and diagnosis/prognosis marker[J].Int J Biochem Mol Biol,2010,1:69-89.
38 De Schrijver E,Brusselmans K,Heyns W,et al.RNA interference-mediated silencing of the fatty acid synthase gene attenuates growth and induces morphological changes and apoptosis of LNCaP prostate cancer cells[J].Cancer Res,2003,63:3799-3804.
39 Zhou W,Simpson PJ,McFadden JM,et al.Fatty acid synthase inhibition triggers apoptosis during S phase in human cancer cells[J].Cancer Res,2003,63(21):7330-7337.

[1]	王晓雅,肖斌,廖扬,唐荣芝,孙朝晖,李林海. CXCR家族蛋白在不同乳腺癌亚型中的表达及临床预后分析[J]. 实用肿瘤学杂志, 2019, 33(3): 206-210.
[2]	李烁,张楠楠,李亮亮,龙志平,尹慧慧,赵亚双,王帆. 外周血白细胞PDE4C基因甲基化及环境因素交互作用与乳腺癌发病的关系[J]. 实用肿瘤学杂志, 2019, 33(3): 233-238.
[3]	李嘉琪,栾瑾微,张,玉,李香兰. 763例三阴性乳腺癌临床病理特征及复发、转移影响因素分析[J]. 实用肿瘤学杂志, 2019, 33(3): 244-249.
[4]	陈艳波, 孔德嘉, 张金锋, 马志刚. 乳腺癌患者CYP2D6基因多态性与他莫昔芬代谢相关性研究[J]. 实用肿瘤学杂志, 2019, 33(2): 110-114.
[5]	孙江宏, 郝明珠, 姜丹, 国飞, 李晓梅. 乳腺炎、良性增生及乳腺癌FFDM鉴别诊断思路[J]. 实用肿瘤学杂志, 2019, 33(2): 139-141.
[6]	马志杰, 王帆, 赵亚双. 乳腺癌化疗患者生存质量及影响因素分析[J]. 实用肿瘤学杂志, 2019, 33(2): 149-154.
[7]	马质莹, 尚乃舰, 蔡妙田, 沈阳, 姜智允. 孕激素及雌激素受体阳性乳腺癌HER-2受体与钼靶影像学特征及临床病理学特征的相关性分析[J]. 实用肿瘤学杂志, 2019, 33(1): 47-51.
[8]	何煦, 叶尚勉, 董丹丹, 李科. HLA-G在乳腺癌中的表达及意义[J]. 实用肿瘤学杂志, 2018, 32(5): 410-414.
[9]	林荣杰, 尹航, 周云峰. ON123300对ER阳性人乳腺癌MCF-7细胞的影响及机制研究[J]. 实用肿瘤学杂志, 2018, 32(3): 193-197.
[10]	李林(综述), 李志高(审校). 二甲双胍与不同分子亚型乳腺癌的关系[J]. 实用肿瘤学杂志, 2018, 32(3): 267-270.
[11]	郑伟, 许守平, 庞达. 长链非编码RNA Linc00152在泛癌中表达、预后及功能研究[J]. 实用肿瘤学杂志, 2018, 32(1): 7-13.
[12]	殷玉莲, 张卫红, 周悦, 叶媚娜, 陈红风. ERα基因单核苷酸多态性与乳腺癌应用芳香化酶抑制剂引发骨丢失的相关性研究[J]. 实用肿瘤学杂志, 2018, 32(1): 14-18.
[13]	黎玉娇, 尚乃舰. 影像学评估乳腺癌新辅助化疗反应的研究进展[J]. 实用肿瘤学杂志, 2018, 32(1): 63-67.
[14]	陈琢, 孔艺然. 沉默UHRF1对乳腺癌细胞增殖和转移的影响[J]. 实用肿瘤学杂志, 2017, 31(6): 512-518.
[15]	李红阳, 孙亮, 姜醒, 苑光军, 刘艳. 蝙蝠葛碱在人乳腺癌MCF-7细胞对5氟尿嘧啶敏感性的研究[J]. 实用肿瘤学杂志, 2017, 31(5): 385-389.