Department of Otolaryngology, Kyorin University School of Medicine, Tokyo, Japan.
Cancer Sci. 2010 Jun;101(6):1382-6. doi: 10.1111/j.1349-7006.2010.01540.x. Epub 2010 Feb 22.
The combination of docetaxel, cisplatin, and fluorouracil significantly enhances the survival of head and neck cancer patients compared to cisplatin and fluorouracil. We hypothesized that docetaxel may affect invasiveness of the head and neck cancer cells in addition to its tumor-killing effect. Two different head and neck cancer cell lines (HEp-2 and Ca9-22) were treated with docetaxel at IC(10) and IC(50) concentrations. Cell migration and invasive growth was evaluated by wound healing assay and three-dimensional (3D) culture of multicellular tumor spheroids, respectively. Expression levels of possible downstream effectors for cell migration/invasiveness were measured by immunoblotting in conditions with or without docetaxel. Docetaxel, but not cisplatin, suppressed filopodia formation compared with no treatment (control) condition. Consistent with this, docetaxel suppressed two-dimensional (2D) cell migration and 3D cell invasion compared with control or cisplatin. Only docetaxel treated cells exhibited thick tubulin bundle and had lower activity of Cdc42, a member of the Rho family of small GTPases. In conclusion, Docetaxel treatment suppressed migration and invasiveness of head and neck cancer cells in vitro, which is likely to be mediated by regulating Cdc42 activity.
多西他赛联合顺铂和氟尿嘧啶可显著提高头颈部癌症患者的生存率，优于顺铂和氟尿嘧啶。我们假设多西他赛可能除了具有肿瘤杀伤作用外，还会影响头颈部癌细胞的侵袭性。用多西他赛的 IC（10）和 IC（50）浓度处理两种不同的头颈部癌细胞系（HEp-2 和 Ca9-22）。通过划痕愈合试验和多细胞肿瘤球体的三维（3D）培养分别评估细胞迁移和侵袭性生长。在用或不用多西他赛的条件下通过免疫印迹法测量可能的细胞迁移/侵袭性的下游效应物的表达水平。与未处理（对照）条件相比，多西他赛而非顺铂抑制了丝状伪足的形成。与此一致，与对照或顺铂相比，多西他赛抑制了 2D 细胞迁移和 3D 细胞侵袭。只有用多西他赛处理的细胞表现出厚的微管束，并且 Cdc42（Rho 家族小 GTPase 的成员）的活性较低。总之，多西他赛治疗在体外抑制了头颈部癌细胞的迁移和侵袭性，这可能是通过调节 Cdc42 活性介导的。
