title: Targeting serum glucocorticoid-regulated kinase-1 in squamous cell carcinoma of the head and neck: a novel modality of local control.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Georgia Regents University, Augusta, GA, United States of America; Palmetto Health/University of South Carolina School of Medicine, Columbia, SC, United States of America.
authors.forename: Henrik O
authors.initials: HO
authors.lastname: Berdel
authors.affiliation: Georgia Regents University, Augusta, GA, United States of America; Plastic Surgery Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Peking, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Yin
authors.affiliation: Georgia Regents University, Augusta, GA, United States of America.
authors.forename: Jun Yao
authors.initials: JY
authors.lastname: Liu
authors.affiliation: Georgia Regents University, Augusta, GA, United States of America.
authors.forename: Karolina
authors.initials: K
authors.lastname: Grochowska
authors.affiliation: Georgia Regents University, Augusta, GA, United States of America.
authors.forename: Christopher
authors.initials: C
authors.lastname: Middleton
authors.affiliation: Georgia Regents University, Augusta, GA, United States of America.
authors.forename: Nathan
authors.initials: N
authors.lastname: Yanasak
authors.affiliation: Georgia Regents University, Augusta, GA, United States of America.
authors.forename: Rafik
authors.initials: R
authors.lastname: Abdelsayed
authors.affiliation: Department of Medicine A, Hematology and Oncology, University Hospital Muenster, Muenster, Germany.
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
authors.affiliation: Georgia Regents University, Augusta, GA, United States of America.
authors.forename: Mahmood
authors.initials: M
authors.lastname: Mozaffari
authors.affiliation: Georgia Regents University, Augusta, GA, United States of America.
authors.forename: Jack C
authors.initials: JC
authors.lastname: Yu
authors.affiliation: Georgia Regents University, Augusta, GA, United States of America.
authors.forename: Babak
authors.initials: B
authors.lastname: Baban
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D017874:Immediate-Early Proteins / Q000037:antagonists & inhibitors*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D000970:Antineoplastic Agents; D020169:Caspases; D002945:Cisplatin; D017874:Immediate-Early Proteins; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D000099184:Serum-Glucocorticoid Regulated Kinases