Targeting serum glucocorticoid-regulated kinase-1 in squamous cell carcinoma of the head and neck: a novel modality of local control

• Published in: PloS one Vol. 9; no. 12; p. e113795
• Main Authors: Berdel, Henrik O, Yin, Hongyu, Liu, Jun Yao, Grochowska, Karolina, Middleton, Christopher, Yanasak, Nathan, Abdelsayed, Rafik, Berdel, Wolfgang E, Mozaffari, Mahmood, Yu, Jack C, Baban, Babak
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 08.12.2014; Public Library of Science (PLoS)
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; Apoptosis; Biology and Life Sciences; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Caspases - metabolism; CD44 antigen; Cell Death; Cell Line, Tumor; Cisplatin; Cisplatin - administration & dosage; Cisplatin - pharmacology; Colon; Colon cancer; Comparative analysis; Disease Models, Animal; Experimental design; Glucocorticoids; Growth rate; Head; Head & neck cancer; Head and neck cancer; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - pathology; Health aspects; Humans; Immediate-Early Proteins - antagonists & inhibitors; Inhibition; Inhibitors; Medicine and Health Sciences; Mice; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - metabolism; Palliation; Prostate cancer; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - pharmacology; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Receptor, ErbB-2 - metabolism; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck; Stem cell transplantation; Stem cells; Steroids (Organic compounds); Tumor Burden - drug effects; Tumor cells; Tumorigenicity; Tumors; Variance analysis; Xenograft Model Antitumor Assays; United States > US; Georgia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0113795

The 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). Human 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. At 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. SGK-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.