Dexamethasone treatment inhibits VEGF production via suppression of STAT3 in a head and neck cancer cell line.
Glucocorticoids (GCs) modulate the synthesis of many pro-inflammatory cytokines and influence multiple transduction pathways. GCs negatively or positively influence the transcription factors of their target genes. All of these transcription signals are closely connected to cancer survival or death. We investigated the action of dexamethasone (DEX) on head and neck cancer cell lines. When SNU-1041 and SNU-1076 were treated with DEX, the cell lines showed different patterns of responses. DEX inhibition of cell growth depended on concentration in SNU-1041, but not in SNU-1076. Furthermore, DEX suppressed vascular endothelial growth factor (VEGF) secretion from SNU-1041, but not from SNU-1076. We explored the mechanism that explains these distinct differences. After DEX treatment, the differences of NF-kappaB (p65), glucocorticoid receptor and p-AKT were not observed between the cell lines. However, phospho-signal transducer and activator of transcription 3 (STAT3) decreased in SNU-1041 only. Moreover, STAT3 inhibition using si-RNA suppressed VEGF secretion. When STAT3 was overexpressed after DEX treatment, the level of VEGF in the culture media was restored. Taken together, we suggest that p-STAT3 can be a mediating factor which regulates VEGF secretion in the DEX treatment. Because the relationship between the three molecules DEX, STAT3 and VEGF is scarcely known, our findings clarified one of the signaling pathways of DEX, which is often used in clinical conditions.
Shim
Seon-Hui
SH
Department of Molecular Tumor Biology, Seoul National University College of Medicine, Seoul, Korea.
Hah
J Hun
JH
Hwang
So-Yeon
SY
Heo
Dae Seog
DS
Sung
Myung-Whun
MW
D015153:Blotting, Western; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D005938:Glucocorticoids / Q000494:pharmacology*; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics
D005938:Glucocorticoids; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D042461:Vascular Endothelial Growth Factor A; D003907:Dexamethasone