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Herceptin对X线照射后乳腺癌细胞DNA-PKcs表达和活性的影响

Effects of Herceptin on DNA-PKcs Expression and Activation in Breast Cancer Cell Line after X-irradiation Exposure

  • 摘要: 目的 观察ERBB2靶向单克隆抗体Herceptin对乳腺癌细胞的辐射后DNA-PKcs表达和活性的影响,探讨其与Herceptin辐射增敏的关系。 方法 通过克隆形成实验检测Herceptin作用对辐射后乳腺癌细胞系MDA-MB-453生存分数(SF)的影响,并且检测Herceptin对辐射后DNA-PKcs蛋白表达和活性的影响,同时通过单细胞中性凝胶电泳分析Herceptin对辐射导致DSB的影响。 结果 Herceptin预处理后进一步降低辐照所致SF值,并且DNA-PKcs蛋白表达和活性明显低于单纯照射组,同时DSB与单纯照射组相比较显著增高。 结论 Herceptin具有对乳腺癌细胞的辐射增敏作用,其可能的分子机制与其抑制DNA-PK活性和蛋白表达导致DSB修复下降有关。

     

    Abstract: Objective To observe the effects of Herceptin on radiation induced DNA-PKcs expression and its activiation in breast cancer cell lines,and elucidate the relationship between herceptin and radiosensitization. Methods Survival fraction differentiation of breast cancer cell line from treatment herciptin was observed after X-irradiation.DNA-PKcs expression was also investigated with Western blot.Double strand break was detected by single cell electrophoretic comet assay. Results Compared with control group,survival fraction of breast cancer cell lines after radiation was significantly decreased,and expression of DNA-PKcs protein increased.Treated with herceptin survival fraction was further decreased with decreased expression of DNA-PKcs protein and activation.However,Double strand break of breast cancer cell lines was further increased. Conclusion Herceptin raised breast cancer cell lines radiosensitization.Its possible mechanism is related to DNA-PKcs expression and activation inhibition and double strand break increase.

     

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