Despite improvements of radiotherapy and better outcomes of cancer patients resistances still limit the therapeutic success. The combined treatment of tumors by the use of irradiation as well as targeted therapies is a promising approach. By the use of a proteomic screening of lung and head and neck cancer cell lines we identified the heat shock protein HSP27 as a potential target protein for a combined treatment strategy.

Overall expression of HSP27 was distinctly lower in HNSCCUM-02T cells which have a high HSP27 phosphorylation ratio, whereas A549 cells revealed the opposite. Irradiation and inhibition of HSP27 phosphorylation by MKII inhibition resulted in a significantly reduced viability in both cell lines. While irradiation impaired migration only in HNSCCUM-02T cells, MKII inhibition exerted that effect in both cell lines. In contrast, knockdown of HSP27 compromised the viability only in A549 cells. Additionally, MKII inhibition counteracts radiation-induced phosphorylation of HSP27 which causes an additive toxicity and reduced migratory capacity in HNSCCUM-02T when combined.

Inhibition of HSP27 expression and phosphorylation in combination with radiotherapy may be an effective treatment option to overcome resistances.

尽管放射疗法的改进和癌症患者的更好结果仍然限制了治疗的成功。通过使用放射治疗和靶向治疗联合治疗肿瘤是一种有前途的方法。通过对肺癌和头颈癌细胞系进行蛋白质组学筛查，我们将热休克蛋白 HSP27 鉴定为联合治疗策略的潜在靶蛋白。

HSP27的总体表达在具有高HSP27磷酸化率的HNSCCUM-02T细胞中明显较低，而A549细胞则相反。通过 MKII 抑制照射和抑制 HSP27 磷酸化导致两种细胞系的活力显着降低。虽然辐射仅在 HNSCCUM-02T 细胞中损害迁移，但 MKII 抑制在两种细胞系中都发挥了这种作用。相比之下，HSP27 的敲低仅在 A549 细胞中损害了活力。此外，MKII 抑制作用可抵消辐射诱导的 HSP27 磷酸化，这会导致 HNSCCUM-02T 的附加毒性和迁移能力降低。

结合放疗抑制 HSP27 表达和磷酸化可能是克服耐药性的有效治疗选择。