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

Henrik O. Berdel, Hongyu Yin, Jun Yao Liu, Karolina Grochowska, Christopher Middleton, Nathan Eugene Yanasak, Rafik A Abdelsayed, Wolfgang E. Berdel, Mahmood S Mozaffari, Jack C Yu, Babak Baban

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Purpose: 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). Experimental Design: 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.

Original languageEnglish (US)
Article numbere113795
JournalPloS one
Volume9
Issue number12
DOIs
StatePublished - Dec 8 2014

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squamous cell carcinoma
glucocorticoids
neck
Tumors
phosphotransferases (kinases)
cisplatin
Cisplatin
Growth
neoplasms
Neoplasms
Cells
Neoplastic Stem Cells
mice
prostatic neoplasms
Therapeutic Uses
Analysis of variance (ANOVA)
Stem cells
colorectal neoplasms
Nude Mice
Design of experiments

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Targeting serum glucocorticoid-regulated kinase-1 in squamous cell carcinoma of the head and neck : A novel modality of local control. / Berdel, Henrik O.; Yin, Hongyu; Liu, Jun Yao; Grochowska, Karolina; Middleton, Christopher; Yanasak, Nathan Eugene; Abdelsayed, Rafik A; Berdel, Wolfgang E.; Mozaffari, Mahmood S; Yu, Jack C; Baban, Babak.

In: PloS one, Vol. 9, No. 12, e113795, 08.12.2014.

Research output: Contribution to journalArticle

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abstract = "Purpose: 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). Experimental Design: 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.",
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T2 - A novel modality of local control

AU - Berdel, Henrik O.

AU - Yin, Hongyu

AU - Liu, Jun Yao

AU - Grochowska, Karolina

AU - Middleton, Christopher

AU - Yanasak, Nathan Eugene

AU - Abdelsayed, Rafik A

AU - Berdel, Wolfgang E.

AU - Mozaffari, Mahmood S

AU - Yu, Jack C

AU - Baban, Babak

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N2 - Purpose: 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). Experimental Design: 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.

AB - Purpose: 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). Experimental Design: 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.

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