Piva Roberto, Belardo Giuseppe, Santoro M Gabriella
Department of Pathology and Center for Experimental Research and Medical Studies (CERMS), University of Turin, Turin, Italy.
Antioxid Redox Signal. 2006 Mar-Apr;8(3-4):478-86. doi: 10.1089/ars.2006.8.478.
Nuclear factor-kappaB (NF-kappaB), a stress-regulated transcription factor belonging to the Rel family, has a pivotal role in the control of the inflammatory and the innate immune responses. Its activation rapidly induces the transcription of a variety of genes encoding cell adhesion molecules, inflammatory and chemotactic cytokines, cytokine receptors, and enzymes that produce inflammatory mediators. More recently, NF-kappaB activation has been connected with multiple aspects of oncogenesis, including the control of cell proliferation, migration, cell cycle progression, and apoptosis. Interestingly, NF-kappaB is constitutively activated in several types of cancer cells, including hematological and epithelial malignancies. In addition, activation of NF-kappaB in cancer cells by chemotherapy or radiation therapy has been associated with the acquisition of resistance to apoptosis, which has emerged as a significant impediment to effective cancer treatment. Selective cyclopentenone inhibitors of the IkappaB kinase, the key enzyme controlling NF-kappaB activation, were recently shown to be potent inducers of apoptosis in chemoresistant lymphoid malignancies. Increasing evidence, summarized in this review, indicates that the development of selective NF-kappaB inhibitors may represent a promising therapeutic tool to sensitize tumor cells to apoptosis and increase the efficacy of conventional anticancer drugs in a wide spectrum of malignancies.
核因子-κB（NF-κB）是一种属于Rel家族的应激调节转录因子，在炎症和固有免疫反应的控制中起关键作用。其激活迅速诱导多种基因的转录，这些基因编码细胞黏附分子、炎症和趋化细胞因子、细胞因子受体以及产生炎症介质的酶。最近，NF-κB激活与肿瘤发生的多个方面相关，包括细胞增殖、迁移、细胞周期进程和细胞凋亡的控制。有趣的是，NF-κB在几种类型的癌细胞中持续激活，包括血液系统和上皮恶性肿瘤。此外，化疗或放疗激活癌细胞中的NF-κB与获得抗凋亡能力相关，这已成为有效癌症治疗的重大障碍。IkappaB激酶是控制NF-κB激活的关键酶，其选择性环戊烯酮抑制剂最近被证明是化疗耐药性淋巴恶性肿瘤中有效的凋亡诱导剂。本综述总结的越来越多的证据表明，选择性NF-κB抑制剂的开发可能是一种有前景的治疗工具，可使肿瘤细胞对凋亡敏感，并提高传统抗癌药物在多种恶性肿瘤中的疗效。
