Motegi K, Azuma M, Aota K, Yamashita T, Tamatani T, Harada K, Yoshida H, Sato M
Department of Oral and Maxillofacial Surgery 2, Tokushima University School of Dentistry, 3 Kuramoto-cho, Tokushima 770-8504, Japan.
Oral Oncol. 2001 Feb;37(2):185-92. doi: 10.1016/s1368-8375(00)00071-3.
Increasing evidence indicates that transcription factor NF-kappaB may play a role in cell survival, and that some chemotherapeutic agents activate NF-kappaB, while inhibition of NF-kappaB renders cells sensitive to these drugs. 5-Fluorouracil (5-FU) exerts its cytotoxic effect through the induction of apoptosis. However, it still remains uncertain whether 5-FU treatment in combination with the inhibition of NF-kappaB largely exerts an anti-proliferative effect on the growth of neoplastic human salivary gland cells. Thus, we investigated whether NF-kappaB suppression in transformed human salivary gland (NS-SV-AC) cells leads to a marked reduction in cell growth in response to 5-FU treatment. Our results demonstrated that under unstimulated conditions, the ability of cell growth in the super-repressor form of IkappaB-alpha (srIkappaB-alpha) cDNA-transfected cell clones (ACMT-6 and -7) was significantly lower than that in the empty vector-transfected cell clone (ACpRc-1). In addition, the growth inhibition caused by 5-FU was greatly enhanced in ACMT-6 and -7 as compared to ACpRc-1. Based on fractional inhibition analysis, this growth inhibition was due to an additive effect of both inhibitors. Electrophoretic mobility shift assay revealed that NF-kappaB activity in these cell clones was not affected by treatment with 5-FU. Accordingly, our data provide evidence that the combination of 5-FU and NF-kappaB suppression cooperatively functions in the growth inhibition of NS-SV-AC cells.
越来越多的证据表明，转录因子核因子-κB（NF-κB）可能在细胞存活中发挥作用，并且一些化疗药物可激活NF-κB，而抑制NF-κB会使细胞对这些药物敏感。5-氟尿嘧啶（5-FU）通过诱导细胞凋亡发挥其细胞毒性作用。然而，5-FU联合抑制NF-κB是否对人涎腺肿瘤细胞的生长产生显著的抗增殖作用仍不确定。因此，我们研究了在转化的人涎腺（NS-SV-AC）细胞中抑制NF-κB是否会导致对5-FU治疗的细胞生长显著减少。我们的结果表明，在未刺激条件下，转染IkappaB-α（srIkappaB-α）cDNA的细胞克隆（ACMT-6和-7）的超抑制形式的细胞生长能力明显低于空载体转染的细胞克隆（ACpRc-1）。此外，与ACpRc-1相比，ACMT-6和-7中5-FU引起的生长抑制大大增强。基于部分抑制分析，这种生长抑制是由于两种抑制剂的相加作用。电泳迁移率变动分析显示，这些细胞克隆中的NF-κB活性不受5-FU处理的影响。因此，我们的数据提供了证据，表明5-FU和NF-κB抑制的联合作用在NS-SV-AC细胞的生长抑制中协同发挥作用。
