Milligan S A, Nopajaroonsri C
Section of Pulmonary Medicine, Medical Service (111P), VA Medical Center, 510 East Stoner Avenue, Shreveport, LA 71101, USA.
Anticancer Res. 2001 Jan-Feb;21(1A):39-44.
Nuclear factor-kappa B (NF-kappa B) nuclear translocation has an important role in preventing apoptotic cell death in some cancers. However, little is known about the role of NF-kB in non-small cell carcinoma.
Human lung adenocarcinoma cells were stimulated with tumor necrosis factor (TNF) alone or TNF with proteasome inhibitors to block NF-kappa B translocation. Cytotoxicity assays, histone-associated DNA-fragmentation ELISA, immunoblots of poly-(ADP ribose)-polymerase (PARP) and electron microscopy were used to evaluate apoptosis.
TNF induced I kappa B proteolysis and NF-kappa B nuclear translocation; however, this was blocked by pretreatment with proteasome inhibitors. TNF alone was not cytotoxic, but when NF-kappa B was blocked TNF induced cell death. Specifically, the cytotoxicity was due to apoptosis as noted by increased DNA-fragmentation, degradation of PARP and characteristic morphology.
Proteasome inhibition was an effective method to inhibit NF-kappa B activation in lung adenocarcinoma cells. TNF in conjunction with. NF-kappa B inhibition was a potent stimulus for apoptosis.
核因子-κB（NF-κB）核转位在某些癌症中对防止凋亡性细胞死亡起重要作用。然而，关于NF-κB在非小细胞癌中的作用知之甚少。
用人肺癌腺癌细胞单独用肿瘤坏死因子（TNF）刺激，或用TNF与蛋白酶体抑制剂共同刺激以阻断NF-κB转位。采用细胞毒性试验、组蛋白相关DNA片段化酶联免疫吸附测定、聚（ADP核糖）聚合酶（PARP）免疫印迹和电子显微镜评估细胞凋亡。
TNF诱导IκB蛋白水解和NF-κB核转位；然而，这被蛋白酶体抑制剂预处理所阻断。单独的TNF无细胞毒性，但当NF-κB被阻断时，TNF诱导细胞死亡。具体而言，细胞毒性是由于凋亡，表现为DNA片段化增加、PARP降解和特征性形态。
蛋白酶体抑制是抑制肺腺癌细胞中NF-κB活化的有效方法。TNF联合NF-κB抑制是凋亡的有力刺激因素。
