Tai Tzong-Shyuan, Lin Pai-Mei, Wu Ching-Fang, Hung Shih-Kai, Huang Chung-I, Wang Chih-Chun, Su Yu-Chieh
Department of Medical Research, E-Da Hospital, Kaohsiung, Taiwan, R.O.C.
School of Medicine, I-Shou University, Kaohsiung, Taiwan, R.O.C.
Anticancer Res. 2019 Feb;39(2):713-720. doi: 10.21873/anticanres.13167.
Radiotherapy (RT) combined with a radiosensitizer represents an important treatment for head and neck squamous cell carcinoma (HNSCC). Only few chemotherapy agents are currently approved as radiosensitizers for targeted therapy. In this study, the potent cyclin-dependent kinase 4/6 (CDK4/6) inhibitor LEE011 was tested for potential to act as a radiosensitizer during RT.
RT enhancement by LEE011 was assessed by in vitro clonogenic assay, flow cytometry, and western blot in a variety of HNSCC cell lines. The HNSCC cell line OML1 and its radiation-resistant clone OML1-R were used.
LEE011 induced cell-cycle arrest in SCC4/SCC25 cells during the G/M phase through inhibition of retinoblastoma protein phosphorylation. LEE011 enhanced the effects of radiation in OML1 cells and overcame radiation resistance in OML1-R cells.
LEE011 is a potential radiosensitizer that can enhance the cytotoxic effects of RT. Clinical trials including LEE011 during RT for HNSCC should be considered.
放射治疗（RT）联合放射增敏剂是头颈部鳞状细胞癌（HNSCC）的一种重要治疗方法。目前仅有少数化疗药物被批准作为靶向治疗的放射增敏剂。在本研究中，对强效细胞周期蛋白依赖性激酶4/6（CDK4/6）抑制剂LEE011在放疗期间作为放射增敏剂的潜力进行了测试。
通过体外克隆形成试验、流式细胞术和蛋白质印迹法，在多种HNSCC细胞系中评估LEE011对放疗的增强作用。使用了HNSCC细胞系OML1及其耐辐射克隆OML1-R。
LEE011通过抑制视网膜母细胞瘤蛋白磷酸化，在G/M期诱导SCC4/SCC25细胞发生细胞周期阻滞。LEE011增强了OML1细胞的放射效应，并克服了OML1-R细胞的辐射抗性。
LEE011是一种潜在的放射增敏剂，可增强放疗的细胞毒性作用。应考虑开展在HNSCC放疗期间纳入LEE011的临床试验。
