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反义缺氧诱导因子-1α对胰腺癌细胞BxPC-3化疗敏感性的影响

Effect of gene transfer of antisense hypoxia inducible factor-1α on chemosensitivity of human pancreatic cancer cell line BxPC-3

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【作者】 常青秦仁义高军冯延平黄涛

【Author】 CHANG Qing,QIN Ren-yi,GAO Jun,FENG Yan-ping,HUANG Tao(Department of Pancreatic-biliary Surgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China)

【机构】 华中科技大学同济医学院附属同济医院胆胰外科华中科技大学同济医学院附属同济医院胆胰外科 湖北武汉430030湖北武汉430030

【摘要】 目的观察反义缺氧诱导因子-1α(HIF-1α)对胰腺癌细胞BxPC-3化疗敏感性的影响。方法实验分组:(1)缺氧条件下(0.5%O2)体外培养4 h,未转染反义HIF-1α质粒的BxPC-3细胞设为缺氧对照组;(2)常氧条件下体外培养,未转染反义HIF-1α质粒的BxPC-3细胞设为常氧对照组;(3)缺氧条件下(0.5%O2)体外培养4 h,稳定转染反义HIF-1α质粒的BxPC-3细胞设为实验组。采用逆转录聚合酶链反应(RT-PCR)和免疫印迹(W estern B lot)检测各组的HIF-1α和survivin表达情况。流式细胞术和MTT比色法检测不同剂量的化疗药物(5-氟尿嘧啶、阿霉素、吉西他宾)对各组的凋亡率和生长抑制率的影响。结果实验组HIF-1α和survivin的表达明显降低(P<0.0 5),与对照组相比,实验组的凋亡率、抑制率与剂量成正比,高剂量引起高抑制(P<0.0 5)。结论反义HIF-1α可能通过阻断survivin的表达而增强胰腺癌对化疗的敏感性。据此可望通过阻断HIF-1α的表达为胰腺癌基因治疗提供一种新途径。

【Abstract】 Objective To observe the effect of antisense hypoxia inducible factor-1α(HIF-1α) on (chemosensitivity) of human pancreatic cancer cell line BxPC-3 under hypoxia. Methods BxPC-3 cells were divided into 3 groups:(1)BxPC-3 cells were non-transfected with antisense HIF-1α plasmid and exposed to 0.5% O2 for 4hr(hypoxia control);(2)normoxic BxPC-3 cells were non-transfected with antisense(HIF-1α) plasmid(normoxia control);(3)BxPC-3 cells were transfected with antisense HIF-1α plasmid and exposed to 0.5% O2 for 4hr(experimental group).Expression of HIF-1α and survivin was detected by RT-PCR and Western Blot.Growth inhibition rates and apoptosis rates of BxPC-3 cells under different(dosages) of chemotherapeutic agents(5-fluorouracil,doxorubicin and gemcitabine) were measured by MTT(colorimetric) assay and flow cytometry (FCM).Results Expression of HIF-1α was obviously down-regulated and at the same time susvivin expression was markedly down-regulated in experimental group(P<0.05).Higher dosages(100 mg/L,200 mg/L and 400 mg/L of 5-fluorouracil,0.05 mg/L,0.075 mg/L and 0.1 mg/L of doxorubicin,10-9 mol/L,10-8 mol/L and 10-7 mol/L of gemcitabine) caused a(greater) increase of inhibition in experimental group than in hypoxia control(P<0.05).Conclusions The results demonstrate that antisense HIF-1α inhibits expression of survivin and enhances chemosensitivity of(human) pancreatic cancer cell BxPC-3.Blocking HIF-1α in pancreatic cancer cells may offer an avenue for gene therapy.

【基金】 国家自然科学基金资助项目(30471693)
  • 【文献出处】 中国普通外科杂志 ,Chinese Journal of General Surgery , 编辑部邮箱 ,2006年06期
  • 【分类号】R735.9
  • 【被引频次】18
  • 【下载频次】91
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