[Phosphorylation of signal transducer and activators of transcription 3 induced by vascular endothelial growth factor in ovarian carcinoma cell line in vitro].
OBJECTIVE
To observe phosphorylation of signal transducer and activators of transcription 3 (STAT3) in Caov-3 induced by vascular endothelial growth factor (VEGF), and to investigate molecular mechanisms of the effect of VEGF on ovarian carcinoma cells.


METHODS
The expressions of phosphorylated STAT3 in Caov-3 induced by VEGF were detected by immunocytochemistry and Western blot methods. Furthermore, the relationship between STAT3 phosphorylation and VEGF stimulation in ovarian carcinoma cells was investigated using a peptide which could specifically bind VEGFR2 and thus block the binding of VEGF to its receptors.


RESULTS
With VEGF stimulation, the expressions of phosphorylated STAT3 were significantly higher than those without VEGF stimulation in Caov-3. And 50 ng/ml was the effective dose resulting in a significant increase of phosphorylated STAT3 (2.20 +/- 0.28/1.37 +/- 0.17) compared to 0 ng/ml (0.56 +/- 0.15/0.47 +/- 0.19) (P < 0.001). Translocation into nuclei of activated STAT3 occurred after 30 min, while STAT3 phosphorylation decreased after 60 min of stimulation (0.95 +/- 0.18/0.66 +/- 0.20). A small peptide specific for VEGFR2, blocked the increase of STAT3 phosphorylation induced by VEGF in a dose dependent manner and 80 micro mol/L was the effective dose (P < 0.001).


CONCLUSIONS
VEGF could induce STAT3 phosphorylation and translocation into nuclei of activated STAT3 in Caov-3, and the small peptide could effectively inhibit these effects of VEGF. It suggests that STAT3 participates in the VEGF signal transduction mediated by VEGFR2 in ovarian carcinoma cells.
Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China.
Fen-fen
FF
Wang
Huai-zeng
HZ
Chen
Xing
X
Xie
Feng
F
Ye
Da-feng
DF
Ye
Wei-guo
WG
Lü
Zhi-ming
ZM
Ding
D000209:Acute-Phase Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology*
D000209:Acute-Phase Proteins; D004268:DNA-Binding Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A