Kim Seong Bum, Kim Jong Soo, Lee Ji Hye, Yoon Won Joon, Lee Dong Seuk, Ko Myoung Seok, Kwon Byung Suk, Choi Dae Hwa, Cho Hong Rae, Lee Byung Ju, Chung Dae Kyun, Lee Hyeon Woo, Park Jeong Woo
Department of Biological Sciences, University of Ulsan, Nam-Gu, Ulsan 680-749, Republic of Korea.
FEBS Lett. 2006 Jan 9;580(1):311-8. doi: 10.1016/j.febslet.2005.12.012. Epub 2005 Dec 12.
This study demonstrates a requirement for NF-kappaB activation in cis-diamminedichloroplatinum (cisplatin)-induced apoptosis in human head and neck squamous cell carcinoma (HNSCC) cell lines. This conclusion was supported by the following observations: cisplatin induced IkappaBalpha degradation and NF-kappaB-dependent transcriptional activation prior to cell death; pyrrolidine dithiocarbamate (PDTC), a chemical inhibitor of NF-kappaB activation, prevented apoptosis; lactacystin, an inhibitor of IkappaBalpha degradation, also prevented apoptosis; and finally, the expression of a super-repressor mutant IkappaBalpha blocked apoptosis. The expression of tumor necrosis factor alpha (TNFalpha) was promoted by cisplatin treatment and was suppressed by PDTC treatment. In addition, a neutralizing antibody against TNFalpha protected cells from cisplatin-induced apoptosis. These findings suggest that NF-kappaB activation is required for cisplatin-induced apoptosis and TNFalpha may play an important role in NF-kappaB-mediated apoptosis in cisplatin-treated HNSCC cell lines.
本研究表明，在顺二氯二氨铂（顺铂）诱导的人头颈鳞状细胞癌（HNSCC）细胞系凋亡过程中，需要激活核因子-κB（NF-κB）。以下观察结果支持了这一结论：顺铂在细胞死亡前诱导IκBα降解和NF-κB依赖的转录激活；吡咯烷二硫代氨基甲酸盐（PDTC），一种NF-κB激活的化学抑制剂，可防止细胞凋亡；蛋白酶体抑制剂乳胞素，一种IκBα降解的抑制剂，也可防止细胞凋亡；最后，超阻遏突变体IκBα的表达可阻断细胞凋亡。顺铂处理可促进肿瘤坏死因子α（TNFα）的表达，而PDTC处理可抑制其表达。此外，抗TNFα中和抗体可保护细胞免受顺铂诱导的凋亡。这些发现表明，顺铂诱导的细胞凋亡需要激活NF-κB，并且TNFα可能在顺铂处理的HNSCC细胞系中NF-κB介导的细胞凋亡中发挥重要作用。
