Department of Oral and Maxillofacial Surgery, Dokkyo Medical University School of Medicine, 880 Kita-kobayashi, Mibu, Shimo-tsuga, Tochigi 321-0293, Japan.
Section of Dentistry and Oral and Maxillofacial Surgery, Sano Kosei General Hospital, 1728 Horigomecho, Sano, Tochigi 327-8511, Japan.
Int J Mol Sci. 2020 Aug 31;21(17):6292. doi: 10.3390/ijms21176292.
Administration of cetuximab (C-mab) in combination with paclitaxel (PTX) has been used for patients with head and neck squamous cell carcinoma (SCC) clinically. In this study, we attempted to clarify the molecular mechanisms of the enhancing anticancer effect of C-mab combined with PTX on oral SCC cells in vitro. We used two oral SCC cells (HSC4, OSC19) and A431 cells. PTX alone inhibited cell growth in all cells in a concentration-dependent manner. C-mab alone inhibited the growth of A431 and OSC19 cells at low concentrations, but inhibited the growth of HSC4 cells very weakly, even at high concentrations. A combined effect of the two drugs was moderate on A431 cells, but slight on HSC4 and OSC19 cells. A low concentration of PTX enhanced the antibody-dependent cellular cytotoxicity (ADCC) induced by C-mab in all of the cells tested. PTX slightly enhanced the anticancer effect of C-mab in this ADCC model on A431 and HSC4 cells, and markedly enhanced the anticancer effect of C-mab on OSC19 cells. These results indicated that PTX potentiated the anticancer effect of C-mab through enhancing the ADCC in oral SCC cells.
西妥昔单抗（C-mab）联合紫杉醇（PTX）已用于临床治疗头颈部鳞状细胞癌（SCC）患者。在这项研究中，我们试图阐明 C-mab 联合 PTX 对体外口腔 SCC 细胞的抗癌作用增强的分子机制。我们使用了两种口腔 SCC 细胞（HSC4、OSC19）和 A431 细胞。PTX 单独以浓度依赖性方式抑制所有细胞的生长。C-mab 单独以低浓度抑制 A431 和 OSC19 细胞的生长，但对 HSC4 细胞的生长抑制作用非常弱，即使在高浓度下也是如此。两种药物的联合作用对 A431 细胞适度，但对 HSC4 和 OSC19 细胞轻微。低浓度的 PTX 增强了所有测试细胞中 C-mab 诱导的抗体依赖性细胞毒性（ADCC）。PTX 略微增强了 ADCC 模型中 C-mab 对 A431 和 HSC4 细胞的抗癌作用，并显著增强了 C-mab 对 OSC19 细胞的抗癌作用。这些结果表明，PTX 通过增强口腔 SCC 细胞中的 ADCC 增强了 C-mab 的抗癌作用。
