Conclusion
Decreased dCK expression promotes NRF2-driven antioxidant transcription, which further enhances gemcitabine treatment resistance, forming a feedback loop.
Methods
By overexpressing dCK in pancreatic cancer cells, we assessed the impact of dCK on NRF2 transcriptional activity. Furthermore, we measured the impact of dCK expression on the intracellular redox balance and reactive oxygen species (ROS) production. By utilizing immunohistochemical staining and tissues from pancreatic cancer patients, we assessed the correlation between dCK and NRF2 expression. Through proliferation and metastasis assays, we examined the impact of dCK expression on cell proliferation and metastasis.
Results
dCK negatively regulates NRF2 transcriptional activity, leading to the decreased expression of ARE-driven antioxidant genes. In addition, dCK negatively regulates intracellular redox homoeostasis and ROS production. Negative correlations between dCK and NRF2 levels in pancreatic cancer cell lines and patient samples were observed. In vitro cell line studies suggested that dCK negatively regulated proliferation and metastasis.