The Effect of Indomethacin on Paclitaxel Sensitivity and Apoptosis in Oral Squamous Carcinoma Cells The Role of Nuclear Factor-κB Inhibition
The Effect of Indomethacin on Paclitaxel Sensitivity and Apoptosis in Oral Squamous Carcinoma Cells The Role of Nuclear Factor-κB Inhibition
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DOI：
10.1001/archoto.2011.131
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发表时间：
2011-08-01
影响因子：
--
通讯作者：
Ondrey, Frank G.
中科院分区：
文献类型：
--
作者：
Caicedo-Granados, Emiro E.;Wuertz, Beverly R.;Ondrey, Frank G.
目的：探讨新的策略，以加强化疗敏感性在头颈部鳞状细胞cancer.Design：口腔鳞状细胞癌细胞核因子-κ B（NF-κ B B）的激活和结合活性紫杉醇，目前使用的药物在头颈部癌症化疗。采用电迁移率改变试验评价吲哚美辛对NF-κ B结合活性的影响。细胞增殖测定用于研究细胞对紫杉醇的敏感性。为研究特异性抑制NF-κ B是否能提高细胞毒活性，在CA-9-22细胞中稳定表达了一种显性负性细胞系--抑制因子κ B-α（I κ B α）。吲哚美辛能够抑制紫杉醇介导的NF-κ B活化，并在24小时促进紫杉醇处理的细胞凋亡。吲哚美辛增强紫杉醇的细胞杀伤作用。显性阴性I κ B α细胞株对紫杉醇的化疗敏感性增加2- 10倍。结论：紫杉醇具有激活口腔鳞癌细胞NF-κ B的能力。吲哚美辛可以逆转这种激活，减少细胞增殖和增加凋亡。联合收割机紫杉醇与吲哚美辛的治疗策略可能通过抑制NF-κ B而具有归因于紫杉醇化学增敏的治疗益处。
Objective: To investigate new strategies to intensify chemosensitivity in head and neck squamous cell carcinoma.Design: Oral squamous carcinoma cells were examined for nuclear factor-kappa B (NF-kappa B) activation and binding activity by paclitaxel, an agent currently used in head and neck cancer chemotherapy. Electromobility shift assays were used to assess the effect of indomethacin on NF-kappa B binding activity. Cell proliferation assays were used to study cell sensitivity to paclitaxel. To examine whether cytotoxicity could be increased by specifically inhibiting NF-kappa B, a dominant negative cell line, inhibitor kappa B-alpha (I kappa B alpha), was stably expressed in CA-9-22 cells.Results: Paclitaxel possessed the capacity to functionally activate NF-kappa B, as demonstrated by luciferase re-porter gene assays and electromobility shift assay. Indomethacin was able to inhibit paclitaxel-mediated NF-kappa B activation and promote apoptosis of paclitaxel-treated cells at 24 hours. Indomethacin augmented the paclitaxel cellkilling effect. The dominant negative I kappa B alpha cell line exhibited increased chemosensitization to paclitaxel by 2-to10-fold.Conclusions: Paclitaxel has the capacity to activate NF-kappa B in oral squamous carcinoma cells. Indomethacin can reverse this activation to decrease cell proliferation and increase apoptosis. Treatment strategies that combine paclitaxel with indomethacin may have therapeutic benefits attributable to paclitaxel chemosensitization through NF-kappa B inhibition.