A selective Aurora A inhibitor, MLN8237, induces cellular Aurora A expression increase and centrosomal abnormality.

• Main Authors: Chih-Ying Chang, 張智瑩
• Other Authors: Ho Lin
• Format: Others
• Language: zh-TW
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/vx29ra

碩士 === 國立中興大學 === 生命科學系所 === 106 === Aurora A is a serine/threonine kinase which primarily localizes in the centrosome and mitotic spindle and responds for centrosome maturation, separation, spindle formation and mitotic entry. Therefore, Aurora A plays an important regulator to mitosis and meiosis as well as the regulation of cell proliferation. The oncogenic role of Aurora A has also been explored in recent years and its inhibition becomes a relevant issue in cancer therapy. MLN8237 (Alisertib) is a specific inhibitor of Aurora A which has been currently under evaluation of cancer clinical trial. In our present results treating the fast-growing cell line, HEK293, with MLN8237 (0-500 nM ), we found the protein levels of Cyclin B1 and Cyclin D1 were increased, suggesting the progress of G2/M phase in cell cycle was affected. It reflects the reason why MLN8237 can be used to treat cancer. Accidentally, the protein levels of Aurora A was significantly increased after MLN8237 treatment. Several lines of evidence also address similar findings without detailed mechanism and discussion. In addition to protein levels, the real time Q-PCR data indicated that Aurora A mRNA (Aurk A) was also increased after MLN8237 treatment. And p53 protein levels and Q-PCR data was also decreased after MLN8237 treatment. In summary, MLN8237 is a potential drug for future cancer therapy; however, the treatment might lead to the increasing gene expression of itself. The physiological negative feedback might be one of the reasons to explain the phenomenon. Meanwhile, the combination treatment against Aurora A expression with its kinase inhibitor might be beneficial to comprehensively block Aurora A actions in cell proliferation inhibition, polyploidy, mitotic catastrophe and multiple centrosome.