CDK4/6 Inhibitor LEE011 Is a Potential Radiation-sensitizer in Head and Neck Squamous Cell Carcinoma: An In Vitro Study

被引：20

作者：

Tai, Tzong-Shyuan ^{[1
]}

Lin, Pai-Mei ^{[2
]}

Wu, Ching-Fang ^{[2
,3
]}

Hung, Shih-Kai ^{[4
]}

Huang, Chung-I ^{[5
]}

Wang, Chih-Chun ^{[6
]}

Su, Yu-Chieh ^{[7
,8
]}

机构：

[1] E Da Hosp, Dept Med Res, Kaohsiung, Taiwan

[2] I Shou Univ, Sch Med, Kaohsiung, Taiwan

[3] E Da Hosp, Div Nephrol, Kaohsiung, Taiwan

[4] Dalin Tzu Chi Hosp, Dept Radiat Oncol, Buddhist Tzu Chi Med Fdn, Chiayi, Taiwan

[5] E Da Canc Hosp, Dept Radiat Oncol, Kaohsiung, Taiwan

[6] E Da Hosp, Dept Otolaryngol, Kaohsiung, Taiwan

[7] Kaohsiung Med Univ Hosp, Div Hematol Oncol, Dept Internal Med, Kaohsiung, Taiwan

[8] Kaohsiung Med Univ, Fac Med, Kaohsiung, Taiwan

来源：

ANTICANCER RESEARCH | 2019年 / 39卷 / 02期

关键词：

CDK4/6; inhibitor; LEE011; radiosensitization; head and neck cancer; radioresistance; CANCER-CELLS; ORAL-CANCER; CYCLE; RADIOSENSITIVITY; PATHWAY;

D O I：

10.21873/anticanres.13167

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: 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. Materials and Methods: 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. Results: LEE011 induced cell-cycle arrest in SCC4/SCC25 cells during the G1/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. Conclusion: LEE011 is a potential radiosensitizer that can enhance the cytotoxic effects of RT. Clinical trials including LEE011 during RT for HNSCC should be considered.

引用

页码：713 / 720

页数：8

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