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阻断PI3K/AKT通路对乳腺癌细胞放射敏感性影响的研究

PI3K/AKT inhibitor influence on the radiosensitivity of breast cancer cells

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【作者】 傅深孙宜章青邵雨卉刘泰福

【Author】 FU Shen~* SUN Yi ZHANG Qing SHAO Yu-hui Liu Tai-fu ~*Department of Radiation Oncology,The Sixth People Hospital,Shanghai Jiaotong University,Shanghai 200332,China

【机构】 上海交通大学附属第六人民医院放疗科上海交通大学附属第六人民医院放疗科复旦大学附属肿瘤医院放疗科

【摘要】 目的研究抑制磷脂酰肌醇3激酶和(或)蛋白激酶B(PI3K/AKT)生存传导路径是否改变乳腺癌细胞的放射敏感性。方法用乳腺癌细胞细胞株MCF7为实验对象,分别接受单纯放射、Ly294002(PI3K抑制剂)和二者结合处理。通过Western印记法证实Ly294002可下调AKT活性。采用成克隆法定量分析细胞增殖性死亡。通过半胱天冬酶-3(caspase-3)活性评估细胞凋亡。结果单纯Ly294002(5μmol/L)可抑制AKT的磷酸化,而单纯放射对AKT的活性无明显影响,二者结合可提高对AKT活性的抑制作用。Ly294002(5μmol/L)在放射前与细胞作用1h及放射后作用10d均可提高MCF7细胞对放射的敏感性。Ly294002结合放射可增加MCF7细胞增殖性死亡,SF4值的放射增敏比为1.25,Do值的放射增敏比为1.42。Ly294002可增加MCF7细胞放射后诱导的细胞凋亡。结论抑制PI3K通过降低AKT活性,增加MCF7细胞对放射的敏感性,为筛选放射敏感剂进行临床实验提供了依据。

【Abstract】 Objective To evaluate whether Ly294002,suppressing phosphatidylinositol 3 kinase (PI3K)/AKT survival signaling pathway,can change the sensitivity of breast cancer cells to radiotherapy. Methods Breast cancer cultured MCF7 cells treated with:radiation alone;Ly294002;or the combination of radiation and Ly294002.The inhibition of PI3K/AKT by Ly294002 was confirmed by Western blot.Clo- nogenic assay was used quantitatively to measure the mitotic cell death,and caspase-3 assay was used to e- valuate apoptosis.Results 1.Ly29400 could partially inhibit phosphorylated AKT but not radiation,the combination of both could enhance the inhibition of phosphorylated AKT,2.Timing of exposing cells to Ly294002 had some impact on clonogenic survival by radiation,one hour pre-radiation and 10 days post-ra- diation exposing to Ly294002 could maximally sensitize the cells to irradiation,3.Ly29400 combined with radiation could synergistically enhance mitotic death and apoptosis of MCF7 cells,with SER of SF4 and D0, being equal to 1.25 and 1.42.Conclusions PI3K/AKT pathway may be a potential target for enhancing the response of breast cancer cells to radiotherapy.

【基金】 上海市卫生局科技发展基金(044017)
  • 【文献出处】 中华放射肿瘤学杂志 ,Chinese Journal of Radiation Oncology , 编辑部邮箱 ,2006年06期
  • 【分类号】R737.9
  • 【被引频次】19
  • 【下载频次】421
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