[1]李卫红,王浩,周晓靓,等.肿瘤放射治疗增敏剂研究新进展[J].国际放射医学核医学杂志,2013,37(4):233-238.[doi:10.3760/cma.j.issn.1673-4114.2013.04.011]
 LI Wei-hong,WANG Hao,ZHOU Xiao-liang,et al.Radiosensitizers development and the pathways[J].International Journal of Radiation Medicine and Nuclear Medicine,2013,37(4):233-238.[doi:10.3760/cma.j.issn.1673-4114.2013.04.011]
点击复制

肿瘤放射治疗增敏剂研究新进展(/HTML)
分享到:

《国际放射医学核医学杂志》[ISSN:1673-4114/CN:12-1381/R]

卷:
37
期数:
2013年第4期
页码:
233-238
栏目:
综述
出版日期:
2013-07-25

文章信息/Info

Title:
Radiosensitizers development and the pathways
作者:
李卫红 王浩 周晓靓 周则卫
300192 天津, 中国医学科学院放射医学研究所, 天津市分子核医学重点实验室
Author(s):
LI Wei-hong WANG Hao ZHOU Xiao-liang ZHOU Ze-wei
Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences, Tianjin 300192, China
关键词:
辐射增敏药分子作用机制抗肿瘤联合化疗方案放射疗法
Keywords:
Radiation-sensitizing agentsMolecular mechanisms of actionAntineoplastic combined chemotherapy protocolsRadiotherapy
DOI:
10.3760/cma.j.issn.1673-4114.2013.04.011
摘要:
目前除传统的亲电子放射增敏剂硝基咪唑类、硝基苯等之外,还发现了部分化疗药物也具有肿瘤放射治疗增敏效果。分子靶向药物的研究方兴未艾,分别作用于组蛋白去乙酰化酶、信号转导子和转录激活因子3、聚腺苷二磷酸核糖基聚合酶、前列腺素H合成酶2、缺氧诱导因子1、核转录因子、热休克蛋白、毛细血管扩张共济失调突变基因等分子靶点,通过各种不同的途径干扰肿瘤DNA修复、抑制肿瘤细胞增殖、促进其凋亡、抑制血管生成从而达到放射增敏效果。
Abstract:
Except for the traditional radiotherapy sensitization agents such as nitro imidazoles and nitrobenzene,some chemotherapeutics also showed sensitization effect.Molecular targeted drug research is in the ascendant,respectively interacting with histone deacetylase,signal transducer and activator of transcription 3,poly (adenosine diphosphate-ribose) polymerase,prostaglandin H synthase-2,(hypoxia inducible factor-1,nuclear factor kappa-light-chain-enhancer of activated B cells,heat shock protein,ataxiatelangiectasia mutated gene and so on,through various ways such as interfering DNA repair,inhibiting tumor cell proliferation,promoting tumor cell apoptosis and inhibiting angiogenesis to improve the sensitivity of cancer cells to iron radiation.

参考文献/References:

[1] Cooper JS, Pajak TF, Forastiere AA, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk sqimmous-cell carcinoma of the head and neck. N Engl J Med, 2004, 350(19):1937-1944.
[2] Bernier J, Domenge C, Ozsahin M, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med, 2004, 350(19):1945-1952.
[3] Zhukov NV, Tjulandin SA. Targeted therapy in the treatment of solid tumors:practice contradicts theory. Biochemistry (Mosc),2008,73(5):605-618.
[4] Longley DB, Harkin DP, Johnston PG. 5-fluorouracil:mechanisms of action and clinical strategies. Nat Rev Cancer, 2003,3(5):330-338.
[5] Spalding AC, Lawrence TS. New and emerging radiosensitizers and radioprotectors. Cancer Invest, 2006,24(4):444-456.
[6] Morgan MA, Parsels LA, Maybaum J, et al. Improving gemcitabine-mediated radiosensitization using molecularly targeted therapy:a review. Clin Cancer Res, 2008, 14(21):6744-6750.
[7] Morgan MA, Parsels LA, Parsels JD, et al. Role of checkpoint kinase 1 in preventing premature mitosis in response to gemcitabine. Cancer Res, 2005, 65(15):6835-6842.
[8] Murphy BA. Topoisomerases in the treatment of metastatic or recurrent squamous carcinoma of the head and neck. Expert Opin Pharmacother, 2005, 6(1):85-92.
[9] Press MF, Lenz HJ. EGFR, HER2 and VEGF pathways:validated targets for cancer treatment. Drugs, 2007, 67(14):2045-2075.
[10] Janku F, Stewart DJ, Kurzrock R. Targeted therapy in non-small-cell lung cancer-is it becoming a reality?. Nat Rev Clin Oncol, 2010,7(7):401-414.
[11] Marks PA. The clinical development of histone deacetylase inhibitors as targeted anticancer drugs. Expert Opin Investig Drugs, 2010, 19(9):1049-1066.
[12] Ree AH, Dueland S, Folkvord S, et al. Vorinostat, a histone deacetylase inhibitor, combined with pelvic palliative radiotherapy for gastrointestinal carcinoma:the Pelvic Radiation and Vorinostat (PRAVO)phase 1 study. Lancet Oncol, 2010, 11(5):459-464.
[13] Shabason JE, Tofilon PJ, Camphausen K. Grand rounds at the National Institutes of Health:HDAC inhibitors as radiation modifiers, from bench to clinic. J Cell Mol Med, 2011, 15(12):2735-2744.
[14] Chen X,Wong P, Radany EH, et al. Suberoylanilide hydroxamic acid as a radiosensitizer through modulation of RAD51 protein and inhibition of homology-directed repair in multiple myeloma. Mol Cancer Res,2012,10(8):1052-1064.
[15] Kim KW, Mutter RW, Cao C, et al. Inhibition of signal transducer and activator of transcription 3 activity results in down-regulation of Survivin following irradiation. Mol Cancer Ther, 2006,5(11):2659-2665.
[16] Johnson GE, Ivanov VN, Hei TK. Radiosensitization of melanoma cells through combined inhibition of protein regulators of cell survival. Apoptosis, 2008, 13(6):790-802.
[17] Chen J,Wang J,Lin L,et al. Inhibition of STAT3 signaling pathway by nitidine chloride suppressed the angiogenesis and growth of human gastric cancer. Mol Cancer Ther, 2012, 11(2):277-287.
[18] L?ser 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. Mol Cancer Ther, 2010, 9(6):1775-1787.
[19] Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature, 2005,434(7035):917-921.
[20] Chalmers AJ, Lakshman M, Chan N, et al. Poly (ADP-ribose)poly-merase inhibition as a model for synthetic lethality in developing radiation oncology targets. Semin Radiat Oncol, 2010, 20(4):274-281.
[21] Che SM, Zhang XZ, Hou L, et al. Cyclooxygenase-2 inhibitor NS398 enhances radiosensitivity of radioresistant esophageal cancer cells by inhibiting AKT activation and inducing apoptosis. Cancer Invest, 2010, 28(7):679-688.
[22] Che SM, Zhang XZ, Liu XL, et al. The radiosensitization effect of NS398 on esophageal cancer stem cell-like radioresistant cells. Dis Esophagus, 2011,24(4):265-273.
[23] Dittmann KH, Mayer C,Ohneseit PA, et al. Celecoxib induced tumor cell radiosensitization by inhibiting radiation induced nuclear EGFR transport and DNA-repair:a COX-2 independent mechanism. Int J Radiat Oncol Biol Phys, 2008, 70(1):203-212.
[24] Grimes KR, Warren GW, Fang F, et al. Cyclooxygenase-2 inhibitor, nimesulide, improves radiation treatment against non-small cell lung cancer both in vitro and in vivo. Oncol Rep, 2006,16(4):771-776.
[25] Solomon SD, Wittes J, Finn PV, et al. Cardiovascular risk of celecoxib in 6 randomized placebo-controlled trials:the cross trial safety analysis. Circulation, 2008, 117(16):2104-2113.
[26] Cerella C, Sobolewski C, Dicato M, et al. Targeting COX-2 expression by natural compounds:a promising alternative strategy to synthetic COX-2 inhibitors for cancer chemoprevention and therapy. Biochem Pharmacol, 2010, 80(12):1801-1815.
[27] H?rdtner C, Multhoff G, Falk W, et al. (-)-Epigallocatechin-3-gallate, a green tea-derived catechin, synergizes with celecoxib to inhibit IL-1-induced tumorigenic mediators by human pancreatic adenocarcinoma cells Colo357. Eur J Pharmacol, 2012, 684(1-3):36-43.
[28] Garg AK, Buchholz TA, Aggarwal BB. Chemosensitization and radiosensitization of tumors by plant polyphenols. Antioxid Redox Signal, 2005,7(11-12):1630-1647.
[29] Nambiar D, Rajamani P, Singh RP. Effects of phytochemicals on ionization radiation-mediated carcinogenesis and cancer therapy. Mutat Res, 2011,728(3):139-157.
[30] Qiao Q, Jiang Y, Li G. Curcumin improves the antitumor effect of X-ray irradiation by blocking the NF-кB pathway:an in-vitro study of lymphoma. Anticancer Drugs, 2012,23(6):597-605.
[31] Veeraraghavan J, Natarajan M, Lagisetty P, et al. Impact of curcumin, raspberry extract, and neem leaf extract on rel protein-regulated cell death/radiosensitization in pancreatic cancer cells. Pancreas, 2011,40(7):1107-1119.
[32] Liu J, Zhang J, Wang X, et al. HIF-1 and NDRG2 contribute to hypoxia-induced radioresistance of cervical cancer Hela cells. Exp Cell Res, 2010,316(12):1985-1993.
[33] Moon SY, Chang HW, Roh JL, et al. Using YC-1 to overcome the radioresistance of hypoxic cancer cells. Oral oncol, 2009, 45(10):915-919.
[34] Harada H, Itasaka S, Zhu Y, et al. Treatment regimen determines whether an HIF-1 inhibitor enhances or inhibits the effect of radiation therapy. Br J Cancer, 2009,100(5):747-757.
[35] Lee K, Zhang H, Qian DZ, et al. Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularization. Proc Natl Acad Sci USA,2009,106(42):17910-17915.
[36] Kim WY, Oh SH, Woo JK, et al. Targeting heat shock protein 90 overrides the resistance of lung cancer cells by blocking radiation-induced stabilization of hypoxia-inducible factor-1alpha. Cancer Res, 2009, 69(4):1624-1632.
[37] Semenza GL. Hypoxia-inducible factor 1(HIF-1) pathway. Sci STKE, 2007, 2007(407):cm8.
[38] Singh-Gupta V,Zhang H, Banerjee S,et al. Radiation-induced HIF-1alpha cell survival pathway is inhibited by soy isoflavones in prostate cancer cells. Int J Cancer, 2009, 124(7):1675-1684.
[39] Shi M, Guo XT, Shu MG, et al. Cell-permeable hypoxia-inducible factor-1(HIF-1)antagonists function as tumor radiosensitizers. Med Hypotheses, 2007, 69(1):33-35.
[40] Yang CM, Lee IT, Lin CC, et al. Cigarette smoke extract induces COX-2 expression via a PKCalpha/c-Src/EGFR, PDGFR/PI3K/Akt/NF-kappaB pathway and p300 in tracheal smooth muscle cells. Am J Physiol Lung Cell Mol Physiol, 2009,297(5):L892-902.
[41] Cheng JC, Chou CH, Kuo ML, et al. Radiation-enhanced hepatocellular carcinoma cell invasion with MMP-9 expression through PI3K/Akt/NF-kappaB signal transduction pathway. Oncogene, 2006, 25(53):7009-7018.
[42] Rudner J,Huiner CE, Handrick R, et al. The Akt-inhibitor Erufosine induces apoptotic cell death in prostate cancer cells and increases the short term effects of ionizing radiation. Radiat Oncol, 2010,5:108.
[43] Kao GD, Jiang Z, Fernandes AM, et al. Inhibition of phosphatidyli-nositol-3-OH kinase/Akt signaling impairs DNA repair in glioblastoma cells following ionizing radiation. J Biol Chem, 2007, 282(29):21206-21212.
[44] Chendil D, Ranga RS, Meigooni D, et al. Curcumin confers radio-sensitizing effect in prostate cancer cell line PC-3. Oncogene, 2004, 23(8):1599-1607.
[45] Sandur SK, Deorukhkar A, Pandey MK, et al. Curcumin modulates the radiosensitivity of colorectal cancer cells by suppressing constitutive and inducible NF-kappaB activity. Int J Radiat Oncol Biol Phys, 2009, 75(2):534-542.
[46] Sung B, Pandey MK, Ahn KS, et al. Anacardic acid (6-nonadecyl salicylic acid), an inhibitor of histone acetyltransferase, suppresses expression of nuclear factor-kappaB-regulated gene products involved in cell survival, proliferation, invasion, and inflammation through inhibition of the inhibitory subunit of nuclear factor-kappa Balpha kinase,leading to potentiation of apoptosis. Blood, 2008, 111(10):4880-4891.
[47] Zand H, Rahimipour A, Salimi S, et al. Docosahexaenoic acid sensitizes Ramos cells to Gamma-irradiation-induced apoptosis through involvement of PPAR-gamma activation and NF-kappaB suppression. Mol Cell Biochem, 2008,317(1-2):113-120.
[48] Wang L, Fu JN, Wang JY, et al. Selenium-containing thioredoxin reductase inhibitor ethaselen sensitizes non-small cell lung cancer to radiotherapy. Anticancer Drugs, 2011, 22(8):732-740.
[49] Taba K, Kuramitsu Y, Ryozawa S, et al. KNK437 downregulates heat shock protein 27 of pancreatic cancer cells and enhances the cytotoxic effect of gemcitabine. Chemotherapy, 2011,57(1):12-16.
[50] Sahin E,Sahin M,Sanlio?lu AD, et al. KNK437, a benzylidene lactam compound, sensitises prostate cancer cells to the apoptotic effect of hyperthermia. Int J Hyperthermia, 2011, 27(1):63-73.
[51] Hickson I,Zhao Y, Richardson CJ, et al. Identification and characterization of a novel and specific inhibitor of the ataxia-telangiec-tasia mutated kinase ATM. Cancer Res, 2004, 64(24):9152-9159.
[52] Won J, Kim M, Kim N, et al. Small molecule-based reversible reprogramming of cellular lifespan. Nat Chem Biol, 2006, 2(7):369-374.
[53] Rainey MD, Charlton ME, Stanton RV, et al. Transient inhibition of ATM kinase is sufficient to enhance cellular sensitivity to ionizing radiation. Cancer Res, 2008,68(18):7466-7474.
[54] Tofilon PJ, Camphausen K. Molecular targets for tumor radiosensitization. Chem Rev, 2009, 109(7):2974-2988.
[55] 王浩,周晓靓,施培基,等. 靶向放射增敏剂的研究进展. 中华放射医学与防护杂志,2011,31(2):243-245.

相似文献/References:

[1]霍小东,王慧星,阎卫亮,等.血管内皮抑制素对125I近距离照射裸鼠肺癌移植瘤的增敏效应研究[J].国际放射医学核医学杂志,2016,40(5):357.[doi:10.3760/cma.j.issn.1673-4114.2016.05.006]
 Huo Xiaodong,Wang Huixing,Yan Weiliang,et al.Sensitization effect of endostatin for 125I brachytherapy on transplanted tumor in nude mice[J].International Journal of Radiation Medicine and Nuclear Medicine,2016,40(4):357.[doi:10.3760/cma.j.issn.1673-4114.2016.05.006]
[2]刘晓秋,周则卫,沈秀,等.放射增敏剂尼可胺对Wistar大鼠致畸作用的研究[J].国际放射医学核医学杂志,2013,37(2):81.[doi:10.3760/cma.j.issn.1673-4114.2013.02.005]
 LIU Xiao-qiu,ZHOU Ze-wei,SHEN Xiu,et al.Study on teratogenicity of Nikean in Wistar rats[J].International Journal of Radiation Medicine and Nuclear Medicine,2013,37(4):81.[doi:10.3760/cma.j.issn.1673-4114.2013.02.005]
[3]黄少祥,樊体强.塞来昔布对非小细胞肺癌移植瘤的辐射增敏实验研究[J].国际放射医学核医学杂志,2013,37(3):150.[doi:10.3760/cma.j.issn.1673-4114.2013.03.006]
 HUANG Shao-xiang,FAN Ti-qiang.Radiosensitization on non-small cell lung cancer induced by celecoxib[J].International Journal of Radiation Medicine and Nuclear Medicine,2013,37(4):150.[doi:10.3760/cma.j.issn.1673-4114.2013.03.006]
[4]刘晓秋,沈秀,王芹,等.尼可胺在大鼠体内的药代动力学研究[J].国际放射医学核医学杂志,2013,37(5):265.[doi:10.3760/cma.j.issn.1673-4114.2013.05.003]
 LIU Xiao-qiu,SHEN Xiu,WANG Qin,et al.Study on pharmacokinetics of NiKeAn in rat[J].International Journal of Radiation Medicine and Nuclear Medicine,2013,37(4):265.[doi:10.3760/cma.j.issn.1673-4114.2013.05.003]
[5]龙伟,吴红英,张晓东,等.血必净辐射防护作用机制的计算机模拟研究[J].国际放射医学核医学杂志,2013,37(6):329.[doi:10.3760/cma.j.issn.1673-4114.2013.06.001]
 LONG Wei,WU Hong-ying,ZHANG Xiao-dong,et al.Computational study for mechanisms of radiation protection effects of Xuebijing[J].International Journal of Radiation Medicine and Nuclear Medicine,2013,37(4):329.[doi:10.3760/cma.j.issn.1673-4114.2013.06.001]
[6]李玉,董丹,阎英.肿瘤辐射增敏机制研究进展[J].国际放射医学核医学杂志,2007,31(1):48.
 LI Yu,DONG Dan,Yah Ying.The development of radiosensitizer mechanisms[J].International Journal of Radiation Medicine and Nuclear Medicine,2007,31(4):48.
[7]顾菲,刘晓秋.肿瘤辐射增敏的分子机制[J].国际放射医学核医学杂志,2006,30(5):298.
 GU Fei,LIU Xiao-qiu.The molecular mechanism of tumor radiosensitizer[J].International Journal of Radiation Medicine and Nuclear Medicine,2006,30(4):298.
[8]张渊琪,赵德善.分化型甲状腺癌的治疗进展[J].国际放射医学核医学杂志,2017,41(2):126.[doi:10.3760/cma.j.issn.1673-4114.2017.02.009]
 Zhang Yuanqi,Zhao Deshan.Advances in the treatment of differentiated thyroid cancer[J].International Journal of Radiation Medicine and Nuclear Medicine,2017,41(4):126.[doi:10.3760/cma.j.issn.1673-4114.2017.02.009]
[9]董正川,段玉清,樊赛军,等.新型辐射增敏药RRx-001[J].国际放射医学核医学杂志,2017,41(3):214.[doi:10.3760/cma.j.issn.1673-4114.2017.03.011]
 Dong Zhengchuan,Duan YuQing,Fan Saijun,et al.A novel radiosensitizer RRx-001[J].International Journal of Radiation Medicine and Nuclear Medicine,2017,41(4):214.[doi:10.3760/cma.j.issn.1673-4114.2017.03.011]

备注/Memo

备注/Memo:
收稿日期:2012-11-22。
基金项目:中国医学科学院放射医学研究所探索基金(ST1322)
通讯作者:周则卫,Email:zhouzewei@irm-cams.ac.cn
更新日期/Last Update: 1900-01-01