Abstract
Abstract Although the anticancer drugs paclitaxel and doxorubicin are commonly used to treat many types of solid tumors, their effectiveness is highly variable due to tumor cell resistance. Therefore, it is important to find mechanisms that can be targeted to increase the sensitivity of cancer cells to antitumor agents such as paclitaxel and doxorubicin. NIMA related kinase 2 (Nek2), a serine/threonine kinase is emerging as an important oncogene because of its regulatory role in mammalian cell mitosis. Thus, regulation of the Nek2 expression levels may prove important as a target for cancer treatment. In this study, we investigated whether drug sensitivity was increased in the triple negative breast cancer cell lines MDA-MB-231 and MDA-MB-468 by using antisense oligonucleotides (ASOs) and siRNA against Nek2. MDA-MB-231 and MDA-MB-468 breast cancer cells transfected with Nek2 siRNA or ASO were exposed to various concentrations of paclitaxel and doxorubicin. Cell viability, cell cycle distribution, and apoptosis were evaluated. We observed that drug susceptibility in these transfected cells was dramatically increased compared with either agent alone. Interestingly, the cell proliferation of the Nek2 ASO transfected breast cancer cells was much lower than the Nek2 siRNA transfected breast cancer cells. Our FACS data showed paclitaxel treated cells transfected with ASOs arrested in G2/M phase as expected due to Nek2 regulatory function in centrosome duplication. We observed that ASOs and siRNA against Nek2 work with paclitaxel and by arresting cells at G2/M and progressing the cells to apoptosis. Our results suggest that these drugs in combination with Nek2 siRNA or ASO treatment greatly improve the sensitivity of cancer cells. Thus, these results provide a possible new strategy for the treatment of breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 604. doi:10.1158/1538-7445.AM2011-604
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