硼替佐米联合表阿霉素对乳腺癌细胞增殖与凋亡的影响

Effects of bortezomib in combination with epirubicin on the proliferation and apoptosis of breast cancer cells

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 effects of bortezomib, a ubiquitin-proteasome pathway inhibitor with cytotoxic activity in multiple myeloma in vitro and vivo, alone and in combination with epirubicin on biological characteristics of breast cancer ceils. Methods Michigan Cancer Foundation-7 （MCF-7） human breast cancer cell lines were cultured with bortezmib （in concentrations of 0.01, 0.10, 1.00, 5.00 and 10.00 μg/mL） alone or plus epitubicin （in concentra- tions of 0.05, 0.25, 0.50, 1.00 and 5.00 μg/mL）. Effects of bortezomib and epirubicin on the proliferation and viability of breast cancer cells were studied by the MTT assay. MCF-7 cells were cultured with 0. 10 μg/mL of bortezomib ＋ 0.50 μg/mL of epirubicin for 24, 48 and 72hours. The cells stained with propidium iodide were detected for cell cycle analysis. Results Bortezomib inhibited cell proliferation to some extent, without showing a dose-or timedependent manner, and it stopped the cell cycle at the G2/M stage. Epirubicin significantly inhibited proliferation of MCF-7 human breast cancer cells in a doseand time-dependent manner, arresting the cell cycle at the S period. A combination of bortezomib and epirubicin could inhibit proliferation of MCF-7 cells at lower concentrations and in shorter time, indicating their synergistic effect. Conclusion Bortezomib and epirubicin have a synergistic effect on the inhibition of MCF-7 human breast cancer cells. The research showed that the dose of epirubicin can be decreased and its sensitivity can be increased if it is applied with bortezomib, thereby enhancing chemotherapeutic effects and reducing adverse effects of the drugs.