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 G2 phase, whereas Tet was able to lower the number of cells arrested in G2 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 G1 and G2 phases by X-rays, and the number of cells arrested in G2 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 G2 checkpoint abrogator and markedly enhances the cytotoxicity of X irradiation in the p53-mutant cancer cells