NF-κB抑制剂与紫杉烷对未分化甲状腺癌细胞凋亡的诱导作用

Inducing effect of the apoptosis of anaplastic thyroid cancer treated with NF-κB inhibitor and Taxanes

目的探讨联合核因子κB(NF-κB)抑制剂和紫杉烷对未分化甲状腺癌(ATC)凋亡的诱导效果。方法应用Western blot鉴定单独或联合用药后ATC细胞内凋亡关键因子(PARP、Caspase 3、XIAP和survivin)的变化。采用Annexin V-FITC/PI双标记染色流式细胞仪鉴定用药后癌细胞的凋亡变化。结果联合紫杉烷和NF-κB抑制剂后PARP失活裂解产物和Capsase 3活化水解产物的增多较单用紫杉烷更加显著(P<0.01),单用紫杉烷会使凋亡抑制因子XIAP和survivin增加,而联合NF-κB抑制剂则可使二者的表达受到明显抑制(P<0.01)。流式细胞仪鉴定亦证明联合用药可产生协同诱导凋亡的效果(P<0.01)。结论NF-κB抑制剂可提高化疗敏感性和化疗疗效。

Objective To study the inducing effect of the apoptosis of anaplastic thyroid cancer treated with NF-KB inhibitor and Taxanes. Methods Western blot was used to determine the changes of key-apoptotic factors （ PARP, Caspase 3, XIAP and survivin）. Flow cytometry with Annexin V-FITC/Propidium Iodide double staining was also used to analyze the induction of apoptosis. Results Western blot showed that compared with single drug treatment, combined treatment induced significantly more cleaved PARP and cleaved Caspase 3 （P 〈0.01 ）. Taxanes could induce anti-apoptotic factors XIAP and survivin, however, combination of NF-κB inhibitor could effectively suppress this effect （ P 〈 0.01 ）. Flow cytometry also confirmed that the combined treatment synergistically induced apoptosis （P 〈 0.01 ）. Conclusion NF-κB inhibitor could effectively enhance chemotherapeutic sensitization and efficacy in anaplastie thyroid cancer cells.