Targeting Serum Glucocorticoid-Regulated Kinase-1 in Squamous Cell Carcinoma of the Head and Neck: A Novel Modality of Local Control |
| |
Authors: | Henrik O Berdel Hongyu Yin Jun Yao Liu Karolina Grochowska Christopher Middleton Nathan Yanasak Rafik Abdelsayed Wolfgang E Berdel Mahmood Mozaffari Jack C Yu Babak Baban |
| |
Institution: | 1. Georgia Regents University, Augusta, GA, United States of America.; 2. Palmetto Health/University of South Carolina School of Medicine, Columbia, SC, United States of America.; 3. Plastic Surgery Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Peking, China.; 4. Department of Medicine A, Hematology and Oncology, University Hospital Muenster, Muenster, Germany.; Ohio State University, United States of America, |
| |
Abstract: | PurposeThe inhibition of serum glucocorticoid-regulated kinase-1 (SGK-1) has been found to decrease growth of colon and prostate cancer cells. The purpose of this study is to evaluate the therapeutic effect of SGK-1 inhibition in head and neck squamous cell carcinoma (SCC).Experimental DesignHuman head and neck tumors (HTB41/43) were established in athymic mice. Growth rates between mice treated with vehicle (PBS) injection (group 1, n = 5), SGK-1 Inhibitor GSK 650394 (group 2, n = 6), systemic cisplatin (group 3, n = 6), and a combination of SGK-1 Inhibitor and cisplatin (group 4, n = 6) were compared using repeated measures one-way ANOVA with Newman-Keuls Multiple Comparison Test. Tumor cells were subsequently submitted to further analyses.ResultsAt the end of the experiment mean tumor sizes were 122.33+/−105.86, 76.73+/−36.09, 94.52+/−75.92, and 25.76+/−14.89 mm2 (mean +/− SD) for groups 1 to 4. Groups 2 and 3 showed decreased tumor growth compared to controls (p<0.001). Group 4 displayed even greater growth suppression (p<0.0001). Importantly, group 4 fared better than group 3 (p<0.001). CD44 expression was reduced in group 2 (p<0.05), and to an even greater extent in groups 3 and 4 (p<0.0025). A trend towards reduction of HER 2 expression was noted in group 4.ConclusionsSGK-1 inhibition suppresses tumor growth, and in combination with systemic cisplatin exceeds the effect of cisplatin alone. Decreased expression of CD44 and HER 2 implies depletion of tumor stem cells, and less tumorigenicity. SGK-1 inhibition represents a potential modality of local control for palliation in advanced cases. |
| |
Keywords: | |
|
|