[1]张配,赵素容,宋乐乐,等.低相对分子质量肝素联合紫杉醇对鼻咽癌细胞侵袭和迁移能力的影响[J].南方医科大学学报,2012,(11):1529.
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低相对分子质量肝素联合紫杉醇对鼻咽癌细胞侵袭和迁移能力的影响()
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《南方医科大学学报》[ISSN:/CN:]

卷:
期数:
2012年11期
页码:
1529
栏目:
出版日期:
2012-11-15

文章信息/Info

Title:
Effect of low-molecular-weight heparin combined with paclitaxel on the invasiveness and migration of nasopharyngeal carcinoma cellsin vitro
作者:
张配赵素容宋乐乐浦龙健蒋志文刘浩蒋琛琛
关键词:
鼻咽癌低相对分子质量肝素紫杉醇侵袭迁移基质金属蛋白酶-9基质金属蛋白酶组织抑制剂-1乙酰肝素酶
Keywords:
nasopharyngeal carcinoma low-molecular-weight heparin paclitaxel invasion migration matrix metalloproteinase-9 tissue inhibitor of matrix metalloproteinase-1 heparanase
摘要:
目的探讨低相对分子质量肝素(LMWH)联合紫杉醇对鼻咽癌细胞侵袭和迁移能力的影响及其相关的分子机制。方法
采用MTT法检测药物对鼻咽癌细胞CNE1、CNE2的增殖抑制效应;细胞划痕实验、Transwell小室法检测细胞的迁移和侵袭能
力;Western blot检测基质金属蛋白酶-9 (MMP-9)和基质金属蛋白酶组织抑制剂-1 (TIMP-1)的表达;ELISA法检测细胞培养液
中乙酰肝素酶(HPA)的表达。结果MTT结果显示,不同浓度LMWH和紫杉醇对鼻咽癌细胞CNE1、CNE2均具有显著的增殖
抑制作用。200 U·ml-1LMWH与0.1μmol·L-1紫杉醇联合作用于CNE1、CNE2细胞24 h的迁移抑制率分别为66.70%、70.53%,
较单用紫杉醇的迁移抑制率明显提高。同时LMWH与紫杉醇联合作用于CNE1、CNE2细胞的侵袭抑制作用也明显高于单用
紫杉醇的作用。LMWH与紫杉醇均可下调MMP-9和HPA的表达,且合用时作用更加明显。结论LMWH具有增强紫杉醇抑
制鼻咽癌细胞侵袭和迁移的作用,其机制可能与下调MMP-9和HPA的表达有关。
Abstract:
ObjectiveTo investigate the effect of low-molecular-weight heparin (LMWH) combined with paclitaxel (PTX) on the
invasiveness and migration of nasopharyngeal carcinoma cells and explore the molecular mechanisms. MethodsMTT assay
was used to detect the growth inhibition induced by LMWH and PTX in CNE1 and CNE2 cells. Wound healing assay and
Transwell migration assay were employed to assess the effects of the drugs on the cell migration, and Transwell invasion assay
was used to evaluate the cell invasiveness. The cellular expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor
of matrix metalloproteinase-1 (TIMP-1) were analyzed by Western blotting. ELISA was used to determine the expression of
heparanase (HPA) in the culture medium of the cells.ResultsMTT assay showed an obvious suppression of CNE1 and CNE2
cell proliferation in response to LMWH and PTX treatments. Treatment with 200 U·ml LMWH combined with 0.1μmol·L PTX
for 24 h resulted in the inhibition rates of migration of 66.70% and 70.53% in CNE1 and CNE2 cells, respectiuely significantly
higher than the rates in cells with PTX treatment alone. The combined treatment with LMWH and PTX for 24 h also caused a
significantly higher inhibition rate of cell invasion than LMWH and PTX alone. LMWH enhanced the down-regulation of
MMP-9 and HPA induced by PTX.ConclusionLMWH can enhance the inhibitory effect of PTX on the migration and invasion
of nasopharyngeal carcinoma cells, the mechanism of which may involve the down-regulation of MMP-9 and HPA expressions

参考文献/References:

[1]Zhou J, Xiao X, Yi H, et al. Upregulation of Gp96 correlates with the radiosensitivity and five-year survival rate of nasopharyngeal carcinoma[J]. ORL J Otorhinolaryngol Relat Spec, 2012, 74(3):164-71.
[2]Huang PY, Mai HQ, Luo DH, et al. Induction-concurrent chemoradiotherapy versus induction chemotherapy and radiotherapy for locoregionally advanced nasopharyngeal carcinoma[J]. Ai Zheng, 2009, 28(10): 1033-42.
[3]Bossi P, Orlandi E, Bergamini C, et al. Docetaxel, cisplatin and 5-fluorouracil-based induction chemotherapy followed by intensity-modulated radiotherapy concurrent with cisplatin in locallyadvanced EBV-related nasopharyngeal cancer[J]. Ann Oncol, 2011,
          22(11): 2495-500.
[4]Zhang W, Yang HC, Wang Q, et al. Clinical value of combined detection of serum matrix metalloproteinase-9, heparanase, and cathepsin for determining ovarian cancer invasion and metastasis[J]. Anticancer Res, 2011, 31(10): 3423-8.
[5]Hiro J, Inoue Y, Toiyama Y, et al. Possibility of paclitaxel as an alternative radiosensitizer to 5-fluorouracil for colon cancer[J]. Oncol Rep, 2010, 24(4): 1029-34.
[6]Mostafa E, Nasar MN, Rabie NA, et al. Induction chemotherapy with paclitaxel and cisplatin, followed by concomitant cisplatin and radiotherapy for the treatment of locally advanced nasopharyngeal carcinoma[J]. J Egypt Natl Canc Inst, 2006, 18(4): 348-56.
[7]Phillips PG, Yalcin M, Cui H, et al. Increased tumor uptake of chemotherapeutics and improved chemoresponse by novelnon-anticoagulant low molecular weight heparin[J]. Anticancer Res, 2011, 31(2): 411-9.
[8]Dredge K, Hammond E, Handley P, et al. PG545, a dual heparanase and angiogenesis inhibitor, induces potent anti-tumour and anti-metastatic efficacy in preclinical models[J]. Br J Cancer, 2011,104(4): 635-42.
[9]Chen Y, Chen Y, Huang L, et al. Evaluation of heparanase and matrix metalloproteinase-9 in patients with cutaneous malignant melanoma[J]. J Dermatol, 2012, 39(4): 339-43.
[10]Kwong DL, Sham JS, Leung LH, et al. Preliminary results of radiation dose escalation for locally advanced nasopharyngealcarcinoma[J]. Int J Radiat Oncol Biol Phys, 2006, 64(2): 374-81.
[11]Ahmad S, Ansari AA. Therapeutic roles of heparin anticoagulantsin cancer and related disorders [J]. Med Chem, 2011, 7(5): 504-17.
[12]Canales JF, Ferguson JJ. Low-molecular-weight heparins: mechan-isms, trials, and role in contemporary interventional medicine[J].Am J Cardiovasc Drugs, 2008, 8(1): 15-25.
[13]Niers TM, Klerk CP, Dinisio M, et al. Mechanisms of heparin induced anti-cancer activity in experimental cancer models [J]. Crit Rev Oncol Hematol, 2007, 61(3): 195-207.
[14]Mousa SA, Petersen LJ. Anti-cancer properties of low-molecular-weight heparin: preclinical evidence[J]. Thromb Haemost, 2009,102(2): 258-67.
[15]Pandita D, Ahuja A, Velpandian T, et al. Characterization andin vitroassessment of paclitaxel loaded lipid nanoparticles formulated using modified solvent injection technique[J]. Pharmazie, 2009, 64(5): 301-10.
[16]Roy R, Yang J, Moses MA. Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer[J]. JClin Oncol, 2009, 27(31): 5287-97.
[17]Lan YY, Hsiao JR, Chang KC, et al. Epstein-Barr virus latent membrane protein 2A promotes invasion of nasopharyngeal carcinoma cells through ERK/Fra-1-mediated induction of matrix metalloproteinase 9[J]. J Virol, 2012, 86(12): 6656-67.
[18]Groblewska M, Siewko M, Mroczko B, et al. The role of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in the development of esophageal cancer[J]. Folia Histochem Cytobiol,2012, 50(1): 12-9.
[19]Farina AR, Cappabianca L, Desantis G, et al. Thioredoxin stimul-ates MMP-9 expression, de-regulates the MMP-9/TIMP-1 equilibrUm and promotes MMP-9 dependent invasion in humanMDA-MB-231 breast cancer cells[J]. FEBS Lett, 2011, 585(20):
            3328-36.
[20]Teoh ML, Fitzgerald MP, Oberley LW, et al. Overexpression of extracellular superoxide dismutase attenuates heparanase expression and inhibits breast carcinoma cell growth and invasion[J]. Cancer Res, 2009, 69(15): 6355-63.
[21]Ilan N, Elkin M, Vlodavsky I. Regulation, function and clinical significance of heparanase in cancer metastasis and angiogenesis [J]. Int J Biochem Cell Biol, 2006, 38(12): 2018-39.
[22]Raman K, Kuberan B. Chemical tumor biology of heparan sulfate proteoglycans[J]. Curr Chem Biol, 2010, 4(1): 20-31.

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更新日期/Last Update: 1900-01-01