γ-tocotrienol enhances the chemosensitivity of human oral cancer cells to docetaxel through the downregulation of the expression of NF-κB-regulated anti-apoptotic gene products.
γ-tocotrienol enhances the chemosensitivity of human oral cancer cells to docetaxel through the downregulation of the expression of NF-κB-regulated anti-apoptotic gene products.
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DOI：
10.3892/ijo.2012.1692
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发表时间：
2013-01
影响因子：
5.2
通讯作者：
Azuma M
中科院分区：
文献类型：
--
作者：
Kani K;Momota Y;Harada M;Yamamura Y;Aota K;Yamanoi T;Takano H;Motegi K;Azuma M
紫杉烷，包括多西紫杉醇，被广泛用于治疗头颈部鳞状细胞癌。然而，多西紫杉醇的胃肠道毒性限制了其大剂量的临床应用。在这项研究中，我们研究了小剂量多西紫杉醇和γ-生育三烯醇联合治疗对口腔癌(B88)细胞的协同抗癌作用。我们用浓度分别为0.5nM和50μM的多西紫杉醇和γ-生育三烯醇处理B88细胞。当两种药物单独以低剂量处理细胞时，未观察到明显的细胞毒作用。然而，同时用两种药物处理细胞几乎完全抑制了细胞的生长。多西紫杉醇可促进B88细胞核因子-κB(NF-κB)p65蛋白的表达，而γ-生育三烯醇略有抑制核蛋白p65蛋白的表达。值得注意的是，两种药物的联合治疗抑制了多西紫杉醇诱导的核p65蛋白表达。凝胶迁移率改变分析显示，这些药物同时作用于B88细胞后，抑制了核因子-κBDNA结合活性。此外，γ-生育三烯醇下调多西紫杉醇诱导的与抑制细胞凋亡相关的核因子-κB调节基因产物的表达。此外，在两种药物处理后，都检测到了启动子caspase-8和-9以及效应子caspase-3的激活。在多西紫杉醇和γ-生育三烯醇联合作用下，细胞发生明显的细胞凋亡，表现为多聚腺苷二磷酸核糖聚合酶(PARP)的裂解和caspase-3的激活导致核碎裂。这些发现表明，与这些药物联合治疗可能会增强口腔癌患者的治疗反应，同时避免与大剂量β-微管蛋白稳定的单一治疗相关的毒性。
Taxanes, including docetaxel, are widely used for the treatment of squamous cell carcinoma of the head and neck. However, the gastrointestinal toxicity of docetaxel has limited its high-dose clinical use. In this study, we examined the synergistic anticancer effects of combined low-dose docetaxel and γ-tocotrienol treatment on human oral cancer (B88) cells. We treated B88 cells with docetaxel and γ-tocotrienol at concentrations of 0.5 nM and 50 μM, respectively. When cells were treated with either agent alone at a low dose, no significant cytotoxic effect was observed. However, the simultaneous treatment of cells with both agents almost completely suppressed cell growth. Whereas docetaxel stimulated the expression of nuclear factor-κB (NF-κB) p65 protein in B88 cells, γ-tocotrienol slightly inhibited the expression of constitutive nuclear p65 protein. Of note, the combined treatment with both agents inhibited docetaxel-induced nuclear p65 protein expression. Electrophoretic mobility shift assay (EMSA) revealed that the simultaneous treatment with these agents suppressed the NF-κB DNA binding activity in B88 cells. In addition, γ-tocotrienol downregulated the docetaxel-induced expression of NF-κB-regulated gene products associated with the inhibition of apoptosis. Furthermore, the activation of initiator caspases, caspases-8 and -9, and the effector caspase, caspase-3, was detected following treatment with both agents. Finally, apoptosis was also clearly observed as demonstrated by the cleavage of poly(ADP-ribose) polymerase (PARP) and nuclear fragmentation through the activation of caspase-3 by combined treatment with docetaxel and γ-tocotrienol. These findings suggest that the combination treatment with these agents may provide enhanced therapeutic response in oral cancer patients, while avoiding the toxicity associated with high-dose β-tubulin stabilization monotherapy.
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多西他赛对头颈部转移性鳞状细胞癌患者的II期研究。
影响因子：
8.8
作者：
Couteau, C;Chouaki, N;Leyvraz, S;Oulid-Aissa, D;Lebecq, A;Domenge, C;Groult, V;Bordessoule, S;Janot, F;De Forni, M;Armand, JP
通讯作者：
Armand, JP
DOI：
10.1016/j.bbrc.2006.07.029
发表时间：
2006-09-15
影响因子：
3.1
作者：
Eitsuka, Takahiro;Nakagawa, Kiyotaka;Miyazawa, Teruo
通讯作者：
Miyazawa, Teruo
影响因子：
15.9
作者：
Baldwin, AS
通讯作者：
Baldwin, AS
影响因子：
64.5
作者：
Liu, XS;Zou, H;Wang, XD
通讯作者：
Wang, XD
影响因子：
5.3
作者：
Naito, Y;Shimozawa, M;Noguchi, N
通讯作者：
Noguchi, N