Didier Christine, Cavelier Cindy, Quaranta Muriel, Demur Cécile, Ducommun Bernard
Institut d'Exploration Fonctionnelle des Génomes, University of Toulouse, 118 route de Narbonne, 31062 Toulouse, France.
Eur J Pharmacol. 2008 Sep 4;591(1-3):102-5. doi: 10.1016/j.ejphar.2008.06.062. Epub 2008 Jun 19.
Polo-Kinase 1 (PLK1) is a key cell cycle regulator that is necessary for checkpoint recovery after DNA damage-induced G2 arrest. We have examined the effects of PLK inhibition in Acute Myelocytic Leukaemia (AML) cells, whose resistance to genotoxic agents is thought to be associated with checkpoint reinforcement. We report that in U937 AML cells, PLK1 participates in checkpoint recovery, and that inhibition of PLK by the GW843682X compound results in mitotic accumulation and apoptosis. We also found that when challenged with VP-16, inhibition of PLK1 prevented U937 cells from checkpoint exit. Finally, we found that treatment with GW843682X slightly reduced genotoxic-induced inhibition of colony formation efficiency of primary leukaemia cells (CFU-L) from AML patients.
Polo激酶1（PLK1）是一种关键的细胞周期调节因子，对于DNA损伤诱导的G2期阻滞解除后的检查点恢复至关重要。我们研究了PLK抑制对急性髓细胞白血病（AML）细胞的影响，其对基因毒性药物的抗性被认为与检查点强化有关。我们报告，在U937 AML细胞中，PLK1参与检查点恢复，并且GW843682X化合物对PLK的抑制导致有丝分裂积累和凋亡。我们还发现，当用依托泊苷（VP-16）处理时，PLK1的抑制阻止U937细胞离开检查点。最后，我们发现用GW843682X处理略微降低了基因毒性诱导的AML患者原代白血病细胞（CFU-L）集落形成效率的抑制。
