Brighton and Sussex Medical School, University of Sussex, Falmer, Brighton, East Sussex, UK.
Exp Hematol. 2011 Mar;39(3):330-8. doi: 10.1016/j.exphem.2010.12.006. Epub 2010 Dec 22.
Polo-like kinase 1 (Plk1) is a regulator of the cell cycle that has been implicated in the pathology of many cancers. We have investigated whether this kinase plays a role in multiple myeloma (MM) using the Plk1 inhibitor BI 2536.
We have used six MM cell lines and six patient-derived samples to determine the effects of the Plk1 inhibitor, BI 2536, on cell viability, apoptosis, and cytokinesis. We have also examined the effect of the microenvironment on these parameters and the effects of BI 2536 in combination with other antimyeloma agents.
We show that MM cell lines and patient samples express PLK1 and that cell death by apoptosis occurs when Plk1 is inhibited. Cells treated with BI 2536 accumulate in the G(2)/M phase of the cell cycle causing endoduplication. The effects of BI 2536 are not abrogated when cells are cultured on extracellular matrix components, in the presence of interleukin-6, or with bone marrow stromal cells.
Plk1 inhibition leads to cell death in MM cell lines and patient myeloma samples. Our data suggest that inhibition of Plk1 may have potential use as a therapeutic strategy in multiple myeloma.
丝氨酸/苏氨酸激酶 Polo 样激酶 1（Plk1）是细胞周期的调控因子，与多种癌症的发病机制有关。我们使用 Polo 样激酶 1 抑制剂 BI 2536 研究了该激酶在多发性骨髓瘤（MM）中的作用。
我们使用 6 株 MM 细胞系和 6 例患者来源的样本，确定 Plk1 抑制剂 BI 2536 对细胞活力、细胞凋亡和胞质分裂的影响。我们还研究了微环境对这些参数的影响以及 BI 2536 与其他抗骨髓瘤药物联合应用的效果。
我们表明 MM 细胞系和患者样本表达 PLK1，当 Plk1 被抑制时会发生细胞凋亡死亡。用 BI 2536 处理的细胞在细胞周期的 G2/M 期积累，导致核内有丝分裂。当细胞在细胞外基质成分上培养、存在白细胞介素 6 或与骨髓基质细胞共培养时，BI 2536 的作用不会被阻断。
Plk1 抑制导致 MM 细胞系和患者骨髓瘤样本中的细胞死亡。我们的数据表明，抑制 Plk1 可能是多发性骨髓瘤治疗策略的潜在用途。
