Paclitaxel in combination with cetuximab exerts antitumor effect by suppressing NF-κB activity in human oral squamous cell carcinoma cell lines
Paclitaxel in combination with cetuximab exerts antitumor effect by suppressing NF-κB activity in human oral squamous cell carcinoma cell lines
复制标题
DOI：
10.3892/ijo.2014.2655
复制
发表时间：
2014-12-01
影响因子：
5.2
通讯作者：
Ueyama, Yoshiya
中科院分区：
文献类型：
--
作者：
Harada, Koji;Ferdous, Tarannum;Ueyama, Yoshiya
在本研究中，我们研究了紫杉醇（PTX）联合西妥昔单抗对口腔鳞状细胞癌（OSCC）的抗肿瘤作用及其增强抗肿瘤活性的机制。与单独使用任一药物相比，用 PTX (0.02 μg/ml) 和西妥昔单抗 (1 μg/ml) 组合治疗 OSCC（HSC2、HSC3 和 HSC4）细胞，可在体外显着抑制细胞生长。此外，Hoechst 33258染色发现，经PTX和西妥昔单抗联合治疗的OSCC细胞中明显发生DNA断裂。此外，PTX 和西妥昔单抗联合治疗降低了 OSCC 细胞中 p65 (NF-κ B) 蛋白的表达。在我们的体内实验中，HSC2荷瘤裸鼠接受PTX（20 mg/kg/天，每周两次，3周）和/或西妥昔单抗（20 mg/kg/天，2次/周，3周）治疗。与单独的 PTX 或西妥昔单抗或未治疗的对照相比，PTX 和西妥昔单抗联合治疗显着抑制了肿瘤生长。在用 PTX 和西妥昔单抗治疗的 HSC2 肿瘤中，TUNEL 阳性细胞表达上调。此外，免疫组织化学染色显示，用 PTX 和西妥昔单抗治疗的 HSC2 肿瘤中 p65 的表达下调。我们的结果表明，西妥昔单抗可能通过下调 PTX 诱导的 p65 表达来增强 PTX 在 OSCC 中的作用。因此，PTX 和西妥昔单抗的联合治疗可能是治疗 OSCC 的一个有前景的选择。
In the present study, we examined the antitumor effect of paclitaxel (PTX) in combination with cetuximab in oral squamous cell carcinoma (OSCC) and the mechanism of its enhanced antitumor activity. Treatment of OSCC (HSC2, HSC3 and HSC4) cells with PTX (0.02 mu g/ml) and cetuximab (1 mu g/ml) combination resulted in a significant inhibition of cell growth in vitro compared to either agent alone. Moreover, it was found by Hoechst 33258 staining that DNA fragmentation markedly occurred in OSCC cells treated with PTX and cetuximab combination treatment. Furthermore, PTX and cetuximab combination treatment reduced the expression of p65 (NF-kappa B) protein in OSCC cells. In our in vivo experiment, HSC2 tumor-bearing nude mice were treated with PTX (20 mg/kg/day, twice/week, 3 weeks) and/or cetuximab (20 mg/kg/day, twice/week, 3 weeks). Tumor growth was significantly suppressed by PTX and cetuximab combined treatment when compared to PTX or cetuximab alone, or the untreated control. TUNEL-positive cells were upregulated in HSC2 tumors treated with PTX and cetuximab. In addition, immunohistochemical staining revealed that expression of p65 was downregulated in HSC2 tumors treated with PTX and cetuximab. Our results indicate that cetuximab may enhance the effect of PTX in OSCC through the downregulation of PTX induced p65 expression. Therefore, the combination of PTX and cetuximab might be a promising option for OSCC treatment.