粉防己碱增加人乳腺癌细胞对X射线敏感性及其机理研究

目的 研究粉防己碱(Tet)与X射线对人乳腺癌细胞的作用和机理。方法 采用克隆形成分析法，流式细胞术，Western Blotting以及分裂指数法进行实验。结果 在p53突变型MCF-7/ADR细胞中，Tet显著增加X射线的杀伤作用，其增敏比为1．5l；在X射线照射后，细胞明显阻滞于G2期，Tet可以降低这种阻滞。而在p53野生型MCF-7细胞中，Tet增加X射线的杀伤作用不明显，增敏比为1．10；在X射线照射后，细胞阻滞于G1期，部分阻滞于G2期，加入Tet，对于这种阻滞作用降低也不明显。进一步研究显示，MCF-7/ADR细胞在受到X射线照射后，其Cyclin Bl与Cdc2蛋白表达水平明显降低；Tet可以逆转X射线对Cyclin Bl与Cdc2蛋白的表达的抑制作用。分裂指数结果显示Tet可以促使阻滞于G2期的MCF-7/ADR细胞进入M期。结论 Tet是一种G2期阻滞清除剂，能显著增加X射线对人乳腺癌细胞的杀伤作用，这种作用在p53突变型细胞中更明显。

Potentiation of radiosensitivity by tetrandrine in human breast cancer cells and its mechanism

Objective\ To investigate the potentiation of radiosensitivity and mechanism by tetrandrine (Tet) in human breast cancer p53\|mutant MCF\|7/ADR and p53\|wt MCF\|7 cells. Methods\ Clonogenic assay,flow cytometry,Western blotting were preformed in this experiment. Results\ The data of clonogenic assay showed that Tet markedly sensitized MCF\|7/ADR cell to X\|rays,and the sensitization enhancement ratio (SER) of Tet was 1 51.Flow cytometry assay showed that exposure of MCF\|7/ADR cells to X\|rays caused cells to arrest in G\-2 phase,whereas Tet was able to lower the number of cells arrested in G\-2 phase.However,in MCF\|7 cells,the potentiation effect of Tet was lower,and its SER was 1 10.MCF\|7 cells were induced to arrest in G\-1 and G\-2 phases by X\|rays,and the number of cells arrested in G\-2 phase abrogated by Tet was less than that in MCF\|7/ADR cells.Furthermore,the results showed that the levels of Cyclin B1 and Cdc2 expression decreased after X\|irradiation,and the mitotic index was lower too.Tet could reverse this decrease and induce X\|ray\|irradiated cells to enter mitosis. Conclusion\ Tet is a potent G\-2 checkpoint abrogator and markedly enhances the cytotoxicity of X irradiation in the p53\|mutant cancer cells.