Inhibition of polo-like kinase 1 (PLK1) additively improves the outcome of ionising irradiation (IR) in colorectal cancer (CRC)

![CDATA[Background. Ionising irradiation (IR) induces DNA damage in cells, leading to cell cycle arrest and apoptosis. PLK1 is a serine/threonine kinase that promotes cell cycle progression. In response to DNA damage response, PLK1 is involved in the cell recovery mechanisms to resume the cell cycle, including mitosis. PLK1 overexpression is associated with poor patient prognosis in CRC. Although PLK1 expression had been reported to be associated with the outcomes of the neoadjuvant radiotherapy in rectal tumour, there is emerging evidence that this may not be important. Aims. This study aimed to investigate the interactions between PLK1 and IR in CRC. Methods. Radiosensitive (HCT116 and SW48) and radioresistant (Colo320DM and T84) CRC cells were studied. PLK1 in the cells was depleted by siRNA. The effects of the knockdown and IR were then analysed by real-time qPCR, western blot, cell survival assays, apoptotic assays and cell cycle analysis. Results. In some CRC cells PLK1 knockdown by siRNA resulted in substantial reduction of cell survival and, increased induction of apoptosis and G2/M blockage in the CRC cells, except T84 cells. These effects were additive in the responsive cells when the treatment was combined with IR. Expression study reveals that the long term PLK1 expression in the radiosensitive cells decreased post-IR, whereas it remained unaffected in the radioresistent cells. Conclusions. PLK1 knockdown additionally improved the effects of IR in some CRC cells, including some radioresistant cells. Moreover, PLK1 expression of CRC cells after IR exposure affects the radiosensitvity of the cells.]]