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PTK787对VEGF及VEGFR-2在急性髓系白血病中表达的影响 被引量:2

Effect of PTK787 on Expression of VEGF and VEGFR-2 mRNA in Myeloid Leukemia
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摘要 目的检测酪氨酸激酶抑制剂PTK787对急性髓系白血病小鼠血清VEGF浓度及其受体VEGFR-2 mRNA表达水平的影响,进一步探讨PTK787抗急性髓性白血病的作用机制。方法建立急性髓系白血病(AML)SCID小鼠模型,采用酶联免疫吸附试验(ELISA)和反转录PCR(RT-PCR)分别动态检测不同时间点正常小鼠、白血病小鼠及PTK787治疗组小鼠外周血清VEGF浓度及其受体VEGFR-2 mRNA表达的水平变化。结果 (1)正常小鼠和患病小鼠均表达VEGF及VEGFR-2 mRNA;(2)患病组外周血清VEGF浓度和VEGFR-2 mRNA的表达均显著高于正常组小鼠(P<0.05),而且随着病程的进展逐渐升高;(3)PTK787治疗组小鼠外周血清VEGF浓度及其受体VEGFR-2 mRNA表达的水平均较患病组明显降低(P<0.05)。结论 PTK78抗急性髓性白血病的作用与降低血清VEGF及其受体VEGFR-2 mRNA表达的水平密切相关。 Objective To determine the effect of PTK787 on the expression of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 mRNA,and further discuss the role of PTK787 on anti-acute myeloid leukemia.Methods The acute myeloid leukemia model was established on 40 severe combined immunodeficiency mice by HL-60 cells transplantation.The mice were divided into five group randomly,the normal group,the sicken group,the treated group with 50mg/kg PTK787,the treated group with 100mg/kg PTK787,the treated group with 200mg/kg PTK787.Logarithmic phase cells were implanted into the sicken group and the treated group by celiac injection.The expression of vascular endothelial growth factor was detected by enzyme linked immunosorbent assay.The expression of vascular endothelial growth factor receptor-2 mRNA was detected by reverse transcription-polymerase chain reaction.Results(1)Expression of vascular endothelial growth factors and vascular endothelial growth factor receptor-2 mRNA were determined on all mice.(2)Compared with the normal group,the mRNA level of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 in the sicken group was significantly and gradually increased with the course of disease.(3)Compared with the sicken group,the expression of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 mRNA of treated group decreased obviously.Conclusion The anti-effect on acute myeloid leukemia of PTK787 is related with the decrease expression of vascular endothelial growth factor and vascular endothelial growth factor receptor-2.
出处 《肿瘤防治研究》 CAS CSCD 北大核心 2010年第8期859-863,共5页 Cancer Research on Prevention and Treatment
基金 广东省卫生厅资助项目(A2003556)
关键词 PTK787 血管内皮生长因子 血管内皮生长因子受体-2 SCID小鼠 急性髓系白血病 PTK787 Vascular Endothelial Growth Factors Vascular Endothelial Growth Factor Receptor-2 SCID mice Acute Myeloid Leukemia
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参考文献13

  • 1Ratajczak MZ, Ratajczak J, Machalinskj B, et al. Role of vas cular endothelial growth factor (VEGF) and placenta-derived growth factor (PIGF) in regulating human haemopoietic cell urowth[J]. Br J Haematol, 1998, 103(4) : 969-979.
  • 2Neufeld G, Gohen T, Gengrinovitch S, et al. Vascular endothelial growth factor (VEGF) and its receptors[J]. FASEB J, 1999, 13(1): 9-22.
  • 3Shibuya M, Ito N, Claesson Welsh L. Structure and function of vascular endothe -lial growth factor receptor-1 and 2[J]. Curr Top Microbiol Immunol, 1999, 237:59-83.
  • 4陈日玲,陈铭珍,叶泉英,田川,王欢.血管内皮生长因子及其受体在急性髓系白血病动物模型中表达的动态分析[J].中国实验血液学杂志,2009,17(4):852-856. 被引量:2
  • 5Yazici YD, Kim S, Jasser SA, et al. Antivascular therapy of oral tongue squamous cell carcinoma with PTK787[J]. Laryngoscope, 2005,115 (12) : 2249-2255.
  • 6Liu Y, Poon RT, Li Q, et al. Both antiangiogenesis-and angio genesis-independent effects are responsible for hepatoceltular carcinoma growth arrest by tyrosine kinase inhibitor PTK787/ ZK222584[J]. Cancer Res, 2005, 65(9):3691-3699.
  • 7Drevs J, Muller-Driver R, Wittig C, et al. PTK787/ZK 222584, a speeific vascular endothelial growth factor-receptor tyrosine kinase inhibitor, affects the anatomy of the tumor vascular bed and the functional vascular properties as detected by dynamic enhanced magnetic resonance imaging[J]. Cancer Res, 2002,15,62(14) :4015-4022.
  • 8Schoenberger J, Grimm D, Kossmehl P, et al. Effects of PTK787/ZK222584, a tyrosine kinase inhibitor, on the growth of a poorly differentiated thyroid carcinoma: an animal study [J]. Endocrino-logy, 2004, 145(3): 1031-1038.
  • 9Goldbrunner RH, Bendszus M, Wood J, et al. PTK787/ ZK222584, an inhibitor of vascular endothelial growth factor receptor tyrosine kinases, decreases glioma growth and vascularization[J]. Neurosurgery, 2004, 55 (2) : 426-432.
  • 10Mesters RM, Padro T, Bieker R, et al. Stable remission afte radministration of the receptor tyrosine kinase inhibitor SU5416 in a patient with refratory acute myeloid leukemia[J]. Blood, 2001, 98 ( 1 ) : 241-243.

二级参考文献14

  • 1费嘉,张洹.VEGF反义核酸对HL-60细胞作用和机制研究[J].中国实验血液学杂志,2004,12(5):640-643. 被引量:3
  • 2Bosma GC, Custer RP, Bosma MJ. A severe combined immuno-deficiency mutation in the mouse. Nature, 1983; 301 : 527 -530.
  • 3Yang ZF, Poon RT, Liu Y, et al. High doses of tyrosine kinase inhibitor PTK787 enhance the efficacy of ischemic hypoxia for the treat- ment of hepatocellular carcinoma : dual effects on cancer cell and angiogenesis . Mol Cancer Ther, 2006 ; 5 : 2261 - 2270.
  • 4Yazici YD, Kim S, Jasser SA, et al. Antivascular therapy of oral tongue squamous cell carcinoma with PTK787. Laryngoscope, 2005 ; 115 : 2249 -2255.
  • 5Bellamy WT, Richter L, Sirjani D, et al. Vascular endothelial cell growth factor is an autocrine promoter of abnormal localized immature myeloid precursors and leukemia progenitor formation in myelodysplastic syndromes. Blood, 2001 ; 97 : 1427 - 1434.
  • 6Padro T, Bieker R, Ruiz S, et al. Overexpression of vascular endo- thelial growth factor(VEGF) and its cetular receptor KDR( VEGFR-2 ) in the bone marrow of patients with acute myeloid leukemia. Leukemia, 2002; 16:1302 - 1310.
  • 7Dias S, Hattori K, Zhu Z, et al. Autocrine stimulation of VEGFR-2 activates human leukemia cell growth and migration. J Clin Invest, 2000; 106:511 -521.
  • 8Katoh O, Takahashi T, Oguri T, et al. Vascular endothelial growth factor inhibits apopotic death in hematopoietic cell after exposure to chemotherapeutic drugs by inducing MCL-1 acting as an antiapoptotic factor. Cancer Res, 1998; 58:5565-5569.
  • 9Koistinen P, Siitonen T, Mantymaa P, et al. Regulation of the acute myeloid leukemia cell line OCI/AML-2 by endothelial nitric Oxide synthase under the control of a vascular endothelial growth factor signaling system. Leukemia, 2001 ; 15 : 1433 - 1441.
  • 10Kuramoto K, Uersaka T, Kimura A, et al. ZK7, a novel zinc finger gene, is induced by vascular endothelial growth factor and inhibits apoptotic death in hematopoietic cell. Cancer Res, 2000; 60:425 - 430.

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  • 1邰明辉,刘兰梅,马仁强,李雪,庞建新,徐江平.丹红注射液一般药理学实验研究[J].第一军医大学学报,2005,25(3):335-338. 被引量:215
  • 2罗海明,陆华栋,余尚才,扬扬.丹红注射液促血管新生作用及其量效关系的实验研究[J].中西医结合心脑血管病杂志,2007,5(6):504-506. 被引量:38
  • 3Zha S,Yegnasubramanian V,Nelson WG. Cyclooxygenases in cancer:progress and perspective[J].Cancer Letters,2004,(01):1-20.
  • 4Bernard MP,Bancos S,Sime PJ. Targeting cyclooxygen ase-2 in hematological malignancies:rationale and promise[J].Current Pharmaceutical Design,2008,(21):2051-2060.
  • 5Hasegawa K,Ohashi Y,Ishikawa K. Expression of cyclooxygenase-2 in uterine endometrial cancer and anti-tumor effects of a selective COX-2 inhibitor[J].International Journal of Oncology,2005,(05):1419-1428.
  • 6Arunasree KM,Roy KR,Anilkumar K. Imatinib-resistant K562 cells are more sensitive to celecoxib,a selective COX-2 inhibitor:Role of COX-2 and MDR-1[J].Leukemia Research,2008,(06):855-864.doi:10.1016/j.leukres.2007.11.007.
  • 7Sobolewski C,Cerella C,Dicato M. The role of cyclooxy genase-2 in cell proliferation and cell death in human malignancies[J].Int J Cell Biol,2010.215158.
  • 8Ding X,Zhu C,Qiang H. Enhancing antitumor effects in pancreatic cancer cells by combined use of COX 2 and 5 LOX inhibitors[J].Biomedicine and Pharmacotherapy,2011,(07):486-490.
  • 9Sminia P,Kuipers G,Geldof A. COX 2 inhibitors act as radiosensitizer in tumor treatment[J].Biomedicine and Pharmacotherapy,2005,(Supple 2):S272-S275.
  • 10Zhang GS,Liu DS,Dai CW. Antitumor effects of celecoxib on K562 leukemia cells are mediated by cell-cycle arrest,caspase-3 activation,and downregulation of Cox-2 expression and are synergistic with hydroxyurea or imatinib[J].American Journal of Hematology,2006,(04):242-255.doi:10.1002/ajh.20542.

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