关键词: 倍半萜烯内酯, 鼻咽肿瘤, 核因子-κB(NF-κB), 信号转导

Abstract: BACKGROUND AND AIM: To elucidate the effect of sesquiterpene lactones on the nuclear factor-kappa B (NF-κB) signal transduction regulation in human nasopharyngeal carcinoma (NPC) cells. MATERIALS AND METHODS: Parthenolide (PN) was used for treatment. Human CNE1 cell line was used to establish the cellular model after induction by TNF-α. The cytoplasmic and nuclear proteins were extracted after treatment by PN. The degradation of IκBα, the activation of p65 subunit and its nuclear translocation, and the DNA binding activity of nuclear activated NF-κB in EMSA assay were evaluated. RESULTS: In negative control group IκBα protein was expressed in the cytoplasm but not in nucleus. In the PN-pretreated group, however, the IκBα protein was increased in cytoplasm and decreased in nuclear protein. Meanwhile in PN-pretreated followed by TNF-α treatment cells, NF-κB p65 subunit level was increased in cytoplasm but was decreased in nuclei, when compared to non-PN-pretreated but TNF-α induction cells. Further EMSA analysis showed that NF-κB binding activity in PN-treated group was significantly lower than that in TNF-α-induced group. The alterations of intracellular NF-κB signal correlated with PN-pretreatment time (0.5－4 h) and in a dose-dependent (5－25 μmol/L) manner. CONCLUSION: PN inhibited the TNF-α-activated NF-κB signal transduction pathway in NPC cells. Such inhibitory effect may be one of the molecular mechanisms associated with the sensitization of NPC to PN-inducible apoptosis.

Key words: sesquiterpene lactones, nasopharyngeal neoplasms, nuclear factor-kappa B, signal transduction