Abstract 1634: Reduced NIMA-related kinase 2 (Nek2) expression levels enhance paclitaxel sensitivity in breast cancer cells

Abstract

Abstract While many clinical trials have shown that the taxane, paclitaxel (Taxol™), is a very powerful anticancer drug, paclitaxel is still controversial in its applicability for cancer treatment because of the resistance of tumor cells to its effects. Therefore, the purpose of this study is to determine whether the sensitivity of paclitaxel is improved with the addition of antisense oligonucleotides (ASO) against NIMA related kinase 2 (Nek2) in the breast cancer cells. Nek2, a serine/threonine kinase is a gene emerging as important to cancer development because of its regulatory role in mammalian cell mitosis. Moreover, abnormally increased Nek2 expression and activity levels are the main trait of various cancer cells. For these reasons, regulation of the Nek2 expression levels may prove important as a target for cancer treatment. Studies suggest that depletion of Nek2 results in mitotic arrest and ultimately leads to apoptosis in cancer cells. Because many cancer cells have demonstrated resistance to anticancer drugs, more effective therapeutic treatments for cancer patients are necessary. To overcome this treatment resistance, gene silencing through ASO has emerged as an attractive alternative. ASO are able to inhibit cancer progression because they bind to and depress, the expression of genes targeted for their involvement in tumor development. There are currently clinical trials using ASO for cancer patients suffering from a variety of cancers such as breast, colon, and prostate. In this study, we investigated drug sensitivity by using plus ASOs targeted against Nek2 to treat breast cancer cells. MDA-MB-468 breast cancer cells transfected with Nek2 ASO were treated with paclitaxel to evaluate cell proliferation, cell cycle distribution, and apoptosis. We detected that MDA-MB-468 cells treated together with Nek2 ASO and paclitaxel showed more synergistic results compared with either agent alone. Nek2 ASO worked with paclitaxel in the arrest of the cell cycle at the G2-M phase and lead to apoptosis as well. This study suggests that Nek2 ASO and paclitaxel combination treatment of cancer cells may strongly improve the sensitivity of cancer cells. Thus, these results possibly provide a new strategy for the treatment of breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1634.