[Ovarian carcinoma cell inhibits T cell JAK-STAT signal transduction pathway, an experimental study].
OBJECTIVE
To investigate the effect of ovarian carcinoma cell on T cell JAK-STAT signal transduction pathway and its role in the ovarian carcinoma induced immunosupression.


METHODS
Human ovarian carcinoma cells of OVCAR3. CAOV3, and SKOV3 lines were cultured. CD8(+) T cells were isolated from the peripheral venous blood of healthy persons. Then the supernatants of these ovarian carcinoma cell lines and RPMI-1640 were added into the culture of CD8(+) T cells (groups I, II, III, and control). Thiazolyl blue (MTT) method was used to detect the growth of CD8(+) T cell. The cell cycle was examined by flow cytometry. The secretion of the Tc1 type cytokine interferon (IFN)-gamma mRNA and the secretion of the Tc2 type cytokine interleukin (IL)-10 mRNA were detected by RT-PCR. The expression of signaling molecules JAK and JAK3 and the phosphorylated activation of STAT3 and STAT5 in the CD8(+) T cell were analyzed by Western blotting.


RESULTS
The absorbance at the wavelength 570 nm of CD8(+) T cell culture was 0.23 +/- 0.03, 0.28 +/- 0.06, and 0.29 +/- 0.05 in the group I, II, and III, all significantly lower than that in the group IV (0.79 +/- 0.07, all P < 0.01). The percentages of CD8(+) T cells at the stage S and stage G(2)/M were lower, and those in stage G(1)/G(0) were higher in groups I, II, and III than in group IV (all P < 0.01). The IFN-gamma expression was significantly lower in groups I, II, and III in comparison with that in group IV. However, the expression of IL-10 was significantly higher in groups I, II, and III in comparison with that in group IV. The expression of JAK3 protein, but not JAK1 protein, was significantly lower in groups I, II, and III in comparison with that in group IV. The phosphorylated activation of STAT5 was suppressed significantly in groups I, II, and III, whereas the phosphorylated activation of STAT3 was suppressed only in group I.


CONCLUSIONS
Ovarian carcinoma may suppress T cell proliferation through inhibition of the JAK-STAT signal transduction pathway, which may be a mechanism of ovarian carcinoma induced immunosuppression.
Wang
Hui
H
Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China.
Xie
Xing
X
Lü
Wei-guo
WG
Ye
Da-feng
DF
Chen
Huai-zeng
HZ
Li
Xiao
X
Cheng
Qi
Q
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000502:physiology*; D005260:Female; D006801:Humans; D053616:Janus Kinase 3; D008894:Milk Proteins; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology*
D004268:DNA-Binding Proteins; D008894:Milk Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3