@article{oai:nagasaki-u.repo.nii.ac.jp:00009102,
 author = {Kim, EunSook and Matsuse, Michiko and Saenko, Vladimir and Suzuki, Keiji and Ohtsuru, Akira and Mitsutake, Norisato and Yamashita, Shunichi},
 issue = {7},
 journal = {Thyroid},
 month = {Jun},
 note = {Background: We previously reported the partial effectiveness of imatinib (also known as STI571, Glivec, or Gleevec) on anaplastic thyroid cancer (ATC) cells. Imatinib is a selective tyrosine kinase inhibitor that has been used for various types of cancer treatments. Recently, several reports have demonstrated that imatinib enhanced the sensitivity of cancer cells to other anticancer drugs. In this study, therefore, we investigated whether imatinib enhances the antitumor activity of docetaxel in ATC cells. Methods: Two ATC cell lines, FRO and KTC-2, were treated with imatinib and/or docetaxel. Cell survival assay and flow cytometry for annexin V were used to assess the induction of apoptosis. Changes of pro- and antiapoptotic factors were determined by Western blot. Nuclear factor-κB (NF-κB) activity was measured by DNA-binding assay. Tumor growth was also investigated in vivo. Results: The combined treatment significantly enhanced apoptosis compared with single treatment. ATC cells themselves expressed high levels of antiapoptotic factors, X-linked inhibitor of apoptosis (XIAP), and survivin. The treatment with docetaxel alone further increased their expressions; however, the combined treatment blocked the inductions. Although imatinib alone had no effect on NF-κB background levels, combined treatment significantly suppressed the docetaxel-induced NF-κB activation. Further, the combined administration of the drugs also showed significantly greater inhibitory effect on tumor growth in mice xenograft model. Conclusions: Imatinib enhanced antitumor activity of docetaxel in ATC cells. Docetaxel seemed to induce both pro- and antiapoptotic signaling pathways in ATC cells, and imatinib blocked the antiapoptotic signal. Thus, docetaxel combined with imatinib emerges as an attractive strategy for the treatment of ATC., Thyroid, 22(7), pp.717-724; 2012},
 pages = {717--724},
 title = {Imatinib enhances docetaxel-induced apoptosis through inhibition of nuclear factor-κB activation in anaplastic thyroid carcinoma cells},
 volume = {22},
 year = {2012}
}