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目的研究蛋白酶体抑制剂硼替佐米单药及与表阿霉素联合应用对乳腺癌细胞生物学活性的影响。方法采用含10%小牛血清的RPMI-1640培养基培养MCF-7乳腺癌细胞,分别加入终浓度为0.01、0.10、1.00、5.00、10.00μg/mL的硼替佐米,终浓度为0.05、0.25、0.50、1.00、5.00μg/mL的表阿霉素,MTT法测细胞生长抑制率;选择药物浓度为0.10μg/mL硼替佐米+0.50μg/mL表阿霉素联合作用于MCF-7细胞,碘化丙啶(PI)染色法测细胞周期变化。结果单独应用硼替佐米可一定程度的抑制MCF-7细胞的生长,其抑制作用未呈现出明显的量效关系和时间效应关系,可使细胞大量停滞在G2-M期;表阿霉素单药对MCF-7细胞具有明显的抑制作用,并呈现出较明显的量效关系和时间效应关系,可使细胞大量停滞在S期;硼替佐米与表阿霉素联合应用时可以明显提高对MCF-7细胞的抑制作用,且在较低剂量和较短时间产生明显的抑制效果。结论硼替佐米与表阿霉素联合应用可增强表阿霉素的化疗敏感性,降低表阿霉素的使用剂量,为临床增强化疗效果、降低化疗不良反应提供了一定的依据。
Objective To study the effect of bortezomib, a proteasome inhibitor, and the combination with epirubicin on the biological activity of breast cancer cells. Methods MCF-7 breast cancer cells were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum. Bortezomib at final concentrations of 0.01, 0.10, 1.00, 5.00 and 10.0 μg / , 0.50, 1.00, 5.00μg / mL of epirubicin, the cell growth inhibition rate was measured by MTT method. The drug concentration of 0.10μg / mL bortezomib + 0.50μg / mL epirubicin was added to MCF-7 cells , Propidium iodide (PI) staining cell cycle changes. Results Bortezomib alone could inhibit the growth of MCF-7 cells to a certain extent. The inhibitory effect did not show a significant dose-effect and time-dependent effect, which could cause cell arrest in G2-M phase. Epirubicin alone The drug has a significant inhibitory effect on MCF-7 cells, and shows a significant dose-effect and time-dependent relationship, can make a large number of cells in the S phase; bortezomib and epirubicin combination can significantly improve the MCF-7 cells, and had a significant inhibitory effect at lower dose and shorter time. Conclusion The combination of bortezomib and epirubicin can enhance the chemotherapy sensitivity of epirubicin and reduce the dose of epirubicin, which may provide some evidences for enhancing the chemotherapy effect and reducing the adverse reaction of chemotherapy.