TY - JOUR
T1 - Targeting serum glucocorticoid-regulated kinase-1 in squamous cell carcinoma of the head and neck
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
N1 - Publisher Copyright:
© 2014 Berdel et al.
PY - 2014/12/8
Y1 - 2014/12/8
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.
UR - http://www.scopus.com/inward/record.url?scp=84915745938&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84915745938&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0113795
DO - 10.1371/journal.pone.0113795
M3 - Article
C2 - 25485633
AN - SCOPUS:84915745938
SN - 1932-6203
VL - 9
JO - PloS one
JF - PloS one
IS - 12
M1 - e113795
ER -