Over-expression of cFos by the Transcription Factors NFATc2 and Sp1 in Pancreatic Cancer Cells

Abstract

Background/Aim: The transcription factors NFATc2 and Sp1 play a key role in the progression of pancreatic cancer because they interact inside the cells and exert their carcinogenic effect through transcriptional modification. Drugs can also induce a variety of oncogenic signalling cascades. The risk of tumour progression and metastasis seems to be significantly increased in the perioperative period. Our research group has previously demonstrated the function of the interaction between NFATc2 and Sp1 in pancreatic cancer and has identified the proto-oncogene cFos as a target gene. We also found that the anaesthetic drug propofol has anti-tumour properties. The aim of the present study was to investigate the effect of propofol on the expression of the transcription factors NFATc2, Sp1 and cFos in the pancreatic cancer cell lines PaTu 8988t and PANC-1 and to analyse the relevance of this effect for the cells. Materials and Methods: Stimulation with propofol and its effects on the expression of NFATc2, Sp1 and cFos were assessed by immunoblot. Cell cycle distribution was analysed by flow cytometry, and cell proliferation was measured with the ELISA BrdU assay. Propofol and siRNA against cFos were used for stimulation. Results: Propofol regulated the expression of NFATc2, Sp1 and cFos. Stimulation with 250 µM or 500 µM propofol decreased NFATc2, Sp1 and cFos signalling in the Western blot analysis. At the same time, propofol significantly inhibited proliferation and activated cell cycle. The same proliferation behaviour was observed after transient cFos inhibition. These effects were potentiated by simultaneous stimulation with propofol and transient inhibition of cFos, further inhibiting cell proliferation. Interestingly, the cell cycle activation observed after stimulation with propofol alone was reversed in both cell lines. Conclusion: Anaesthetists only see oncological patients in a short time window. However, the perioperative period is increasingly recognised as a very vulnerable time with a major impact on tumour progression. Further studies are needed to identify the underlying mechanisms and to verify their clinical relevance, especially in anaesthesia.