NF-κB抑制剂与紫杉烷联合靶向性化疗在未分化甲状腺癌治疗中的应用  

Combined Therapy of Molecular-Oriented NF-κB Inhibitor and Taxanes on Anaplastic Thyroid Cancer Cells

作　　者：孟召伟[1] 董峰[1] 谭建[1] 

机构地区：[1]天津医科大学总医院核医学科,300052

出　　处：《天津医药》2009年第9期730-733,共4页Tianjin Medical Journal

基　　金：天津医科大学科研课题(项目编号:2008KY20)

摘　　要：目的:研究核因子κB(NF-κB)抑制剂和紫杉烷对未分化甲状腺癌(ATC)的联合治疗机制。方法:应用细胞存活分析法研究单独或联合应用DHMEQ和紫杉烷后ATC细胞的凋亡情况;通过DNA结合实验分析药物作用后核内NF-κB与其特异的寡聚核苷酸探针结合能力的变化;应用Western blot鉴定药物作用后ATC细胞内凋亡关键因子(PARP和Caspase3)的变化。结果:细胞存活分析法证明联合用药组与单独用药组比较存活的ATC细胞显著减少(P<0.01);紫杉烷诱导ATC细胞NF-κB增高,而预先用NF-κB抑制剂预处理1h可以有效地抑制这种现象,按时程在紫杉烷作用0、2、4、8、12和24h时间点的差异均有统计意义(P<0.01);Western blot证实联合用药后PARP的失活裂解产物和Capsase3的活化水解产物明显增多。结论:紫杉烷在诱导ATC凋亡的同时会导致ATC细胞NF-κB的增高从而削弱其疗效,当与NF-κB抑制剂联合使用可以获得协同的疗效。Objective： To study the anti-tumor activity of nuclear factor-kappaB （NF-κB）inhibitor and taxanes in anaplastic thyroid cancer（ATC） cells and the molecular mechanism thereof. Methods： The cell survival assay was performed to assess the apoptosis. The agents＇ effects on NF-κB＇ s signaling were assessed by DNA-binding assay and the nuclear NF-κB protein changes were detected by Western blot. Changes of key-apoptotic factors were also determined by Western blot. Results： It was found that taxanes induced NF-κB activation in ATC cells. However, NF-κB inhibitor completely suppressed the DNA binding capacities of NF-κB and lowered the levels of nuclear NF-κB protein. Compared to single treatment, the combined treatment synergistically induced apoptosis, confirmed by cell survival assay and Western blot. Conclusion： These findings demonstrate that although taxanes are potent chemotherapeutic drugs, their NF-κB inducing abilities in tumor cells can attenuate anti-tumor activities. However, NF-κB inhibitor can effectively suppress this phenomenon and increase chemosensitivity and enhance apoptosis in ATC ceils synergistically.

关 键 词：甲状腺肿瘤 NF—κB 紫杉烷类 细胞凋亡 抗肿瘤联合化疗方案 细胞 培养的 

分 类 号：R73-3[医药卫生—肿瘤] R736.1[医药卫生—临床医学]