Regulation of UT-OC-3 ovarian carcinoma cells by cytokines: inhibitory effects on cell proliferation and activation of transcription factors AP-1 andNF-kappa B
M. Seppanen et al., Regulation of UT-OC-3 ovarian carcinoma cells by cytokines: inhibitory effects on cell proliferation and activation of transcription factors AP-1 andNF-kappa B, EUR J ENDOC, 142(4), 2000, pp. 393-401
The present study was designed to investigate the growth regulatory effects
of cytokines in UT-OC-3 ovarian cystadenocarcinoma cells in vitro. The eff
ects of interleukin-6 (IL-6), interferons alpha (IFN-alpha) and gamma (IFN-
gamma), granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour n
ecrosis factor alpha (TNF-alpha), and transforming growth factor beta 1 (TG
F-beta 1) were investigated by I-125-deoxyuridine ((125)IUdR) incorporation
assay. In order to understand better the molecular mechanisms of the obser
ved effects, the activation of DNA-binding proteins was studied by electrop
horetic mobility shift assay. In addition, cellular DNA was tested by fragm
entation analysis to determine if the most growth inhibitory cytokines are
able to induce programmed cell death (apoptosis). After 48 h in culture, TG
F-beta 1, TNF-alpha, IFN-alpha and IL-6 showed a clear inhibitory effect on
(125)IUdR incorporation (P < 0.005), and IFN-gamma and GM-CSF caused even
more significant inhibition (P < 0.001). IFN-alpha and IFN-gamma were both
growth inhibitory after 72 h in culture (P < 0.005). Similarly, GM-CSF indu
ced a slight inhibition (P < 0.05); whereas TGF-beta 1 and TNF-alpha almost
blocked DNA synthesis (P < 0.001) after 72 h. IL-6 had no statistically si
gnificant effect on cell proliferation after 72 h. Transcription factors AP
-1 and NF-kappa B were both constitutively expressed in UT-OC-3 cells. The
binding activity of AP-1 was found to be stimulated by the growth inhibitor
y cytokines, TGF-beta 1 and TNF-alpha, and the binding of NF-kappa B was st
imulated by TNF-alpha. Apoptosis does not seem to be induced by any of thes
e cytokines in the UT-OC-S ovarian cancer cell model.