1. PI3k inhibitors (BKM120 and BYL719) as radiosensitizers for head and neck squamous cell carcinoma during radiotherapy
- Author
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Fu-Cheng Chuang, Shyh-An Yeh, Yu-Chieh Su, Tzer-Zen Hwang, Chih-Chun Wang, and Jian-Han Chen
- Subjects
Radiation-Sensitizing Agents ,medicine.medical_treatment ,Cancer Treatment ,Aminopyridines ,Phosphatidylinositol 3-Kinases ,Cell Signaling ,Medicine and Health Sciences ,Phosphoinositide-3 Kinase Inhibitors ,Staining ,Multidisciplinary ,Cell Staining ,Crystal Violet Staining ,Head and Neck Tumors ,Neoplasm Proteins ,Oncology ,Head and Neck Neoplasms ,Carcinoma, Squamous Cell ,Medicine ,Research Article ,Signal Transduction ,Clinical Oncology ,Signal Inhibition ,Science ,Morpholines ,Radiation Therapy ,Surgical and Invasive Medical Procedures ,Research and Analysis Methods ,Head and Neck Squamous Cell Carcinoma ,Radioresistance ,Cell Line, Tumor ,Carcinoma ,medicine ,Humans ,Radiosensitivity ,Squamous Cell Carcinoma ,Survival rate ,PI3K/AKT/mTOR pathway ,business.industry ,Cancers and Neoplasms ,Biology and Life Sciences ,Cell Biology ,medicine.disease ,Head and neck squamous-cell carcinoma ,Otolaryngological Procedures ,Radiation therapy ,stomatognathic diseases ,Thiazoles ,Head and Neck Cancers ,Cell culture ,Specimen Preparation and Treatment ,Cancer research ,Clinical Medicine ,business - Abstract
Approximately 500,000 new cases of head and neck squamous cell carcinoma (HNSCC) are reported annually. Radiation therapy is an important treatment for oral squamous cell carcinoma (OSCC). The survival rate of patients with HNSCC remained low (50%) in decades because of radiation therapy failure caused by the radioresistance of HNSCC cells. This study aimed to identify PI3K inhibitors that can enhance radiosensitivity. Results showed that pan-Phosphoinositide 3-kinases (PI3K) inhibitor BKM120 and class I α-specific PI3K inhibitor BYL719 dose-dependently reduced the growth of OSCC cells but not that of radioresistant OML1-R cells. The combination treatment of BKM120 or BYL719 with radiation showed an enhanced inhibitory effect on OSCC cells and radioresistant OML1-R cells. Furthermore, the enhanced inhibitory effect of the combination treatment was confirmed in patient-derived OSCC cells. The triple combination treatment of mTOR inhibitor AZD2014 and BKM120 or AZD2014 and BYL719 with radiation showed a significantly enhanced inhibitory effect on radioresistant OML1-R cells. These results suggest that the PI3K inhibitors are potential therapeutic agents with radiosensitivity for patients with OSCC.
- Published
- 2021