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乙酰肝素酶反义寡核苷酸对人胰腺癌细胞侵袭力的抑制作用 被引量:11

Transfection of antisense oligodeoxynucleotide inhibits heparanase gene expression and invasive ability of human pancreatic cancer cell line in vitro and in vivo
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摘要 目的探讨HPSE AS-ODN对人胰腺癌细胞HPSE基因、蛋白表达及体内、外侵袭力的抑制作用。方法用脂质体将HPSE AS-ODN转染Panc-1细胞,逆转录-聚合酶链反应(RT- PCR)和Western印迹法分别检测转染后HPSE mRNA和蛋白表达;Transwell法检测体外侵袭力。建立裸鼠皮下Panc-1肿瘤模型,按10 mg/kg体重瘤体内注射AS-ODN隔日1次×10。治疗结束后断颈处死裸鼠,剥瘤称重,计算抑瘤率。结果 AS-ODN组mRNA和蛋白表达受到明显抑制,体外侵袭细胞数(个/视野)为60.00±9.31,体内平均瘤重(g)为1.860±0.505;对照组和NS-ODN组体外侵袭细胞数分别为253.00±9.35和240.75±9.36,体内平均瘤重分别为2.948±0.483和2.768± 0.615。AS-ODN组与对照组相比差异有统计学意义(P<0.01)。结论 AS-ODN抑制人胰腺癌细胞 HPSE mRNA和蛋白的表达,并降低癌细胞的侵袭力。 Objective To investigate the inhibitory effects of heparanase (HPSE) antisense oligodeoxynudeotide (AS-ODN) on HPSE gene expression and invasive ability of human pancreatic cancer cell line Pane-1 in vitro and in vivo. Methods HPSE AS-ODN was transfected into Panc-1 cells with liposome. RT-PCR and Western blot were performed to detect the expression of HPSE mRNA and protein, respectively. The invasive ability in vitro was evaluated by invasion chamber assay. The models of human pancreatic cancer subcutaneous xenograft in nude mice were established. HPSE AS-ODN and nonsense oligodeoxynucleotide (NS-ODN) were injected into xenograft, respectively. After treatment, the tumor weight was measured and tumor growth inhibitory rate was calculated. Results The expression of HPSE mRNA and protein of Panc-1 cells treated with AS-ODN were significantly inhibited. The average number of invasion cells of AS-ODN group in vitro was 60.00 ± 9.31, significantly less than 253.00 ± 9.35 in control group and 240.75 ± 9.36 in NS-ODN group. The average weight of xenografts in AS- ODN group in vivo was (1.860±0.505) g, (2.948±0.483) g in control group and (2.768 ±0.615) g in NS-ODN group respectively. Conclusion HPSE AS-ODN inhibits HPSE mRNA and protein expression, and reduces the invasive ability of Panc-1 in vitro and in vivo.
出处 《中华实验外科杂志》 CAS CSCD 北大核心 2006年第4期570-572,共3页 Chinese Journal of Experimental Surgery
关键词 寡核苷酸类 反义 乙酰肝素酶 侵袭 胰腺癌 Oligodeoxynucleotide, antisense Heparanase Invasion Pancreatic carcinoma
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参考文献5

  • 1Koliopanos A,Friess H,Kleeff J,et al.Heparanase expression in primary and metastatic pancreatic cancer.Cancer Res,2001,61:4655-4659.
  • 2Rohloff J,Zinke J,Schoppmeyer K,et al.Heparanase expression is aprognostic indicator for postoperative survival in pancreatic adenocarcinoma.Br J Cancer,2002,86:1270-1275.
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  • 5张友磊,傅志仁,陈学云,杨佳荟,王元和,沈茜.乙酰肝素酶反义寡核苷酸对人乳腺癌细胞株侵袭力的抑制作用[J].中华实验外科杂志,2004,21(3):367-369. 被引量:9

二级参考文献4

  • 1Tamm I,Dorken B,Hartmann G.Aantisense therapy in oncology: new hope for an old idea[].The Lancet.2001
  • 2Vlodavsky I,Friedmann Y,Elkin M,et al.Mammalian heparanase: gene cloning, expression and function in tumor progression and metastasis[].Nature Medicine.1999
  • 3Crooke ST.Potential roles of antisense technology in cancer chemotherapy[].Oncegene.2000
  • 4Hulett MD,Freeman C,Hamdorf RT,et al.Cloning of mammalian heparanase, an important enzyme in tumor invasion and metastasis[].Nature Medicine.1999

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