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环氧化酶-2抑制剂塞来昔布对胃癌端粒酶活性影响的体内外实验研究 被引量:5

Study on the Effects of Telomerase Activity by Selective COX-2 Inhibitor Celecoxib in Gastric Cancer in Vitro and in Vivo
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摘要 目的探讨选择性环氧合酶-2(COX-2)抑制剂塞来昔布对SGC-7901人胃癌细胞及裸鼠移植瘤的生长、端粒酶活性及相关因素的影响,研究其抗肿瘤的作用机制。方法终浓度为100,200,及300μmol/L的塞来昔布作用于SGC-7901人胃癌细胞,同时建立裸鼠胃癌模型,20只裸鼠随机分为两组,对照组隔日腹腔注射生理盐水,塞来昔布组隔日腹腔注射塞来昔布30mg/kg,采用MTT比色法测定胃癌细胞的生长抑制率,采用半定量-TRAP银染法检测SGC-7901人胃癌细胞及裸鼠移植瘤组织中的端粒酶活性。结果不同浓度的塞来昔布对SGC-7901人胃癌细胞的生长均有抑制作用,抑制率与对照组相比,差异有显著性(P<0.05);塞来昔布组裸鼠肿瘤生长明显受抑制,抑瘤率为61.3%,与对照组相比,差异有显著性(P<0.05);同时塞来昔布也显著抑制SGC-7901人胃癌细胞及裸鼠移植瘤组织中的端粒酶活性,其抑制作用呈时间-剂量依赖性。结论塞来昔布通过降低端粒酶活性,诱导细胞凋亡,抑制细胞增殖,从而参与抑制胃癌生长,这可能是COX-2抑制剂体内抗胃癌的机制之一。 Objective To study the effects of celecoxib,a selective COX-2 inhibitor,on cell proliferation and telomerase activi- ty in SGC-7901 human gastric cancer cell line and mice xenograft to explore its anti-neoplasm mechanism. Methods MTT assay was used to determine cell proliferation after incubation in different concentrations (100,200,300 μmol/L) of celecoxib. Twenty mice xenograft models with SGC-7901 human gastric cancer cell were established and randomly divided into two groups. The mice of treated groups were administered with selective COX-2 inhibitor celecoxib. Telomerase activity was detected by semi-TRAP assay. Results Celecoxib inhibited significantly the growth of SGC-7901 human gastric cancer cells and xenograft. It elevated the inhibit- ing rate(P 〈 0.05)as compared with control groups. The telomerase activity was significantly inhibited in SGC-7901 human gastric cancer cells and xenngraft in dose and time dependent manner. Conclusion COX-2 inhibitor celecoxib inhibited telomerase activity, induced apoptosis and inhibited proliferation,The results indicate one of the mechanisms underlying the anti-cancer effect of COX-2 inhibitor.
出处 《实用癌症杂志》 2006年第2期113-116,共4页 The Practical Journal of Cancer
基金 青岛市卫生局科研基金资助(2004-wszd005)
关键词 环氧合酶-2 胃癌 SGC-7901细胞 裸鼠 端粒酶 抑制剂 Cyclooxygenase-2(COX-2) Gastric cancer SGC-7901 cell Node mice Telomerase Inhibitor
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参考文献11

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二级参考文献10

  • 1Fosslien E. Biochemistry of cyclooxygenase(COX)-2 inhibitors and molecular pathology of COX-2 in neoplasia[J]. Crit Rev Clin Lab Sci, 2000,37(5) : 431.
  • 2Lynch PM. COX-2 inhibition in clinical cancer prevention[J]. Oncology ,2001,15(3) :21.
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  • 4Tatsuguchi A, Matsui K, Shinji Y, et al. Cyclooxygenase-2 expression correlates with anglogenesis and apoptoslsin gastric cancer tissue [J]. Hum Pathol, 2004,35 (4) :488.
  • 5Buttitta F, Pellegrini C, Marchetti A, Human telomerase reverse transcriptase mRNA expression assessed by realtime reverse transcription polymerase chain reaction predicts chemosensitivity in patients with ovarian carcinoma[J].J Clin Onco1,2003,21(7):1320.
  • 6Nishimura G,Yanoma S, Satake K, et al. An experimental model of tumor dormancy therapy for advanced head and neck carcinoma[J].Jpn J Cancer Res,2000,91(11) :1199.
  • 7Akre K, Ekstrom AM, Signorello LB, et al. Aspirin and risk for gastric cancer:a population-based case-control study in Sweden[J]. Br J Cancer,2001,84(7) :965.
  • 8Jacoby RF, Seibert K, Cole CE, et al. The cyclooxygenase-2 inhibltorcelecoxib is a potent preventive and therapeutic agent in the rain mouse model of adenomatous polyposiss[J]. Cancer Res, 2000,60(18) :5040.
  • 9Reddy BS,Hirose Y, Lubet R, et al. Chemoprevention of colon cancer by specific cyclooxygenase-2 inhibitorcelecoxib administered during different stages of carcinogenesis[J]. Cancer Res, 2000,60 (2) : 293.
  • 10Shureiqi I, Chen D, Lotan R, et al. 15-Lipoxygenase-1 mediates nonsteroidal anti-inflammatory drug-induced apoptosis independently of cyclooxygenase-2 in coloncancer cells[J]. Cancer Res ,2000,60(24) :6846.

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