关键词: 未分化甲状腺癌, 多烯紫杉醇, 核因子κB抑制剂, TUNEL凋亡染色

Abstract: Objective: We sought to study if Dehydroxymethylepoxyquinomicin (DHMEQ), a novel NF-κB inhibitor, can enhance docetaxel’s anti-tumor activity in anaplastic thyroid cancer (ATC) cells (FRO) xenograft in nude mice test. Methods: FRO xenograft nu/nu mice models were created by injecting 5×106 cells on both flanks. The dosages of drugs were determined as intraperitoneal (i.p.) injection with 5 mg/kg of docetaxel once a week; daily i.p. injection with 6mg/kg of DHMEQ for two weeks; combined treatment was given with both drugs, and control group mice received vehicle injections only. One day after treatment, TUNEL apoptotic staining was performed on excised tumor tissues. Tumor dimensions were monitored for 32 days. Results: Although any drug was able to delay tumor growth, the combined treatment of DHMEQ and docetaxel for two weeks was much more effective. The TUNEL apoptotic staining showed drug-treatment induced many positively stained cells, while the combined regiment tremendously increased positively stained cells. Conclusion: For the first time the treatment of docetaxel combined with NF-κB inhibitor were tried on ATC-cell xenograft in vivo models. Docetaxel is able to induce NF-κB signaling pathway in cancer cells, which could attenuate anti-tumor activities of the drugs, but NF-κB inhibitor can effectively suppress this phenomenon and create chemo-sensitive environment and synergistically enhance apoptosis.

Key words: anaplastic thyroid cancer, docetaxel, nuclear factor-κB inhibitor, TUNEL apoptotic staining