Effect of polo-like kinase 1 gene silence on cell cycle and drug resistance in K562/A02 cell

摘要

Polo-like kinase 1(PLK1) plays an important role in many cell-cycle-related events. At G_2/M transition, PLK1 contributes to the activation of cyclinB/Cdc by phosphorylation of Cdc25C, centrosome functional maturation, bipolar spindle formation. In later stage of mitosis, PLK1 is involved in regulating components of the anaphase-promoting complex (APC) for mitotic exit and in the execution of cytokinesis. Moreover, recent reports have shown that PLK1 is involved in both G_2 and mitotic DNA damage checkpoints. When G_2/M DNA damage occurs, PLK1 activity is suppressed and cell cycle arrests to repair the damaged DNA. So far, the deregulated expression of PLK1 has been detected in many types of human tumors and PLK1 is considered as a novel prognostic marker for several tumors. Non-small- cell lung cancer (NSCLC) patients whose tumor showed that high PLK1 expression had poorly curative effect, and were resistant to chemotherapy, which implied that PLK1 might be associated with drug resistance. K562/A02 is a classical multidrug resistant (MDR) human tumor cell line with the overexpression of the drug efflux protein, P-glycoprotein encoded by multidrug resistance 1 (mdr1) gene. We took advantage of vector-based small RNA interfering technique to specifically deplete PLK1 in K562/A02 cells for investigating the functions of PLK1 in cell cycle progression and drug resistance.