HER2 结合亲和体分子 (Z(HER2∶342))₂ 增加 SKBR-3 细胞的放射敏感性。
The HER2-binding affibody molecule (Z(HER2∶342))₂ increases radiosensitivity in SKBR-3 cells.
机构信息
Department of Radiology, Oncology and Radiation Sciences, Division of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
出版信息
PLoS One. 2012;7(11):e49579. doi: 10.1371/journal.pone.0049579. Epub 2012 Nov 14.
We have previously shown that the HER2-specific affibody molecule (Z(HER2∶342))₂ inhibits proliferation of SKBR-3 cells. Here, we continue to investigate its biological effects in vitro by studying receptor dimerization and clonogenic survival following irradiation. We found that (Z(HER2∶342))₂ sensitizes the HER2-overexpressing cell line SKBR-3 to ionizing radiation. The survival after exposure to (Z(HER2∶342))₂ and 8 Gy (S(8Gy) 0.006) was decreased by a factor four compared to the untreated (S(8Gy) 0.023). The low HER2-expressing cell line MCF-7 was more radiosensitive than SKBR-3 but did not respond to (Z(HER2∶342))₂. Treatment by (Z(HER2∶342))₂ strongly increased the levels of dimerized and phosphorylated HER2 even after 5 minutes of stimulation. The monomeric Z(HER2∶342) does not seem to be able to induce receptor phosphorylation and dimerization or sensitize cells to irradiation.
我们之前已经表明，HER2 特异性亲和体分子（Z(HER2∶342)）抑制 SKBR-3 细胞的增殖。在这里，我们通过研究照射后受体二聚化和集落存活，继续在体外研究其生物学效应。我们发现，（Z(HER2∶342)）使过表达 HER2 的 SKBR-3 细胞系对电离辐射敏感。与未处理组相比，暴露于（Z(HER2∶342)）和 8 Gy（S(8Gy) 0.006）后，存活（S(8Gy) 0.023）降低了四倍。低表达 HER2 的 MCF-7 细胞系比 SKBR-3 更敏感，但对（Z(HER2∶342)）没有反应。即使在刺激 5 分钟后，（Z(HER2∶342)）的治疗也强烈增加了二聚化和磷酸化 HER2 的水平。单体 Z(HER2∶342)似乎不能诱导受体磷酸化和二聚化，也不能使细胞对辐射敏感。
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