Polo-Like Kinase 1 Pharmacological Inhibition as Monotherapy or in Combination: Comparative Effects of Polo-Like Kinase 1 Inhibition in Medulloblastoma Cells

Abstract

Background: Medulloblastoma (MB) is a common malignant brain tumor in children. Although survival rates have improved, long-term side effects from treatment remain a significant challenge. To mitigate these effects, researchers are continually seeking new therapeutic targets. Polo-like kinase 1 (PLK1) is a crucial regulator of the cell cycle and is often overexpressed in proliferative cells. Its inhibition has been proposed as a potential oncological strategy.

Objectives: This study aimed to assess and compare the effects of PLK1 inhibition both alone and in combination with existing radio- and chemotherapy treatments in MB cells.

Methods: We treated UW402, UW473, ONS-76, and DAOY MB cell lines with PLK1 inhibitors BI 2536, BI 6727, GW843682X, and GSK461364. We evaluated various parameters, including cell proliferation, apoptosis, clonogenicity, invasion, adhesion, and cell cycle distribution. Additionally, we assessed the combinatorial effects of these inhibitors with gamma irradiation or with the chemotherapeutic agents etoposide, cisplatin, and temozolomide.

Results: PLK1 inhibition led to a notable reduction in cell proliferation, clonogenic capacity, invasion, and adhesion, with only minor differences between the inhibitors. All four inhibitors induced G2/M cell cycle arrest and increased cell death. PLK1 inhibition significantly enhanced the sensitivity of MB cells to radiation, though results were less pronounced when combined with chemotherapy.

Conclusions: Our findings demonstrate that PLK1 inhibitors effectively exert anti-mitotic effects on MB cells and can enhance radiosensitivity. These results support the potential of targeting PLK1 to improve therapeutic strategies for BI 2536 medulloblastoma.