Department of Oral Biology, College of Dentistry, University of Nebraska Medical Center, Lincoln, Nebraska, USA.
Head Neck. 2010 May;32(5):636-45. doi: 10.1002/hed.21234.
Resistance to chemotherapy is a major limitation in the treatment of head and neck squamous cell carcinomas (HNSCCs), accounting for high mortality rates in patients. Here, we investigated the role of replication protein A (RPA) in cisplatin and etoposide resistance.
We used 6 parental HNSCC cell lines. We also generated 1 cisplatin-resistant progeny subline from a parental cisplatin-sensitive cell line, to examine cisplatin resistance and sensitivity with respect to RPA2 hyperphosphorylation and cell-cycle response.
Cisplatin-resistant HNSCC cell levels of hyperphosphorylated RPA2 in response to cisplatin were 80% to 90% greater compared with cisplatin-sensitive cell lines. RPA2 hyperphosphorylation could be induced in the cisplatin-resistant HNSCC subline. The absence of RPA2 hyperphosphorylation correlated with a defect in cell-cycle progression and cell survival.
Loss of RPA2 hyperphosphorylation occurs in HNSCC cells and may be a marker of cellular sensitivities to cisplatin and etoposide in HNSCC.
对头颈鳞状细胞癌（HNSCC）的化疗耐药是治疗的主要限制因素，导致患者死亡率高。在这里，我们研究了复制蛋白 A（RPA）在顺铂和依托泊苷耐药中的作用。
我们使用了 6 种亲本 HNSCC 细胞系。我们还从亲本顺铂敏感细胞系中产生了 1 个顺铂耐药的衍生亚系，以研究 RPA2 过度磷酸化和细胞周期反应对顺铂耐药和敏感性的影响。
与顺铂敏感细胞系相比，顺铂耐药 HNSCC 细胞中对顺铂的过度磷酸化 RPA2 的水平增加了 80%至 90%。可以在顺铂耐药的 HNSCC 亚系中诱导 RPA2 过度磷酸化。缺乏 RPA2 过度磷酸化与细胞周期进程和细胞存活缺陷相关。
RPA2 过度磷酸化的缺失发生在 HNSCC 细胞中，可能是 HNSCC 细胞对顺铂和依托泊苷敏感性的标志物。
