Cancer Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Department of Oncology, Affiliated Hospital of Chengde Medical College, Chengde, Hebei 067000, China.
Biosci Rep. 2020 Feb 28;40(2). doi: 10.1042/BSR20194167.
Radiation therapy is a widely used treatment for esophageal cancer. However, radiation resistance might result in a poor prognosis. Overexpression of HER2 has been related to adaptive radiation resistance. Pyrotinib is a HER2 inhibitor that shows an anti-tumor effect in breast cancer. The present study aims to explore the influence of pyrotinib combined with radiotherapy on HER2-positive esophageal cancer cells and explore the underlying mechanism. We screened two cell lines (TE-1 and KYSE30) that highly express HER2 from several human esophageal cancer cell lines. Cells were treated with pyrotinib or/and radiation. Cell proliferation, cell cycle distribution, and cell migration were measured. The protein levels involved in cell cycle and DNA repair were measured by Western blot. Results showed that pyrotinib inhibited HER2 activation and exerted an anti-proliferative effect in TE-1 and KYSE30 cells. Furthermore, it enhanced the anti-proliferative effect of radiation in these two cell lines. These effects might be via inhibiting HER2 phosphorylation, inducing G0/G1 arrest, and reducing EMT and DNA repair. Our results indicated that pyrotinib sensitivitied HER2 positive esophageal cancer cells to radiation treatment through various mechanisms. These findings may provide a new therapeutic strategy for treating HER2 positive esophageal cancer.
放射疗法是治疗食管癌的常用方法。然而，放射抵抗可能导致预后不良。HER2 的过表达与适应性放射抵抗有关。吡咯替尼是一种 HER2 抑制剂，在乳腺癌中显示出抗肿瘤作用。本研究旨在探讨吡咯替尼联合放射治疗对 HER2 阳性食管癌细胞的影响，并探讨其潜在机制。我们从几种人食管癌细胞系中筛选出两种高表达 HER2 的细胞系（TE-1 和 KYSE30）。用吡咯替尼或/和放射处理细胞。测量细胞增殖、细胞周期分布和细胞迁移。通过 Western blot 测量参与细胞周期和 DNA 修复的蛋白水平。结果表明，吡咯替尼抑制 HER2 激活，并在 TE-1 和 KYSE30 细胞中发挥抗增殖作用。此外，它增强了这两种细胞系中放射的抗增殖作用。这些作用可能是通过抑制 HER2 磷酸化、诱导 G0/G1 期阻滞以及减少 EMT 和 DNA 修复来实现的。我们的结果表明，吡咯替尼通过多种机制使 HER2 阳性食管癌细胞对放射治疗敏感。这些发现可能为治疗 HER2 阳性食管癌提供新的治疗策略。
