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.