EIF5A regulates proliferation and chemoresistance in pancreatic cancer through the sHH signalling pathway.

BACKGROUND

Pancreatic cancer (PC) has a very poor prognosis and comparatively short survival. Eukaryotic translation initiation factor 5A (EIF5A) promotes cancer metastasis. Here, we exploited the biological role of EIF5A in PC chemoresistance.

METHODS

Expression of EIF5A was analysed in PC cells and tissues by real-time PCR, Western blotting, immunohistochemistry and immunofluorescent. EIF5A expression was specifically suppressed by transfection, and subsequently the alterations of growth behaviour and resistance to anticancer treatment were tested in an orthotopic tumour model.

RESULTS

The results showed EIF5A was increased in human PC tissues and PC cells. We found EIF5A knockdown reduced the PC proliferation ability in vivo and in vitro. In addition, sonic hedgehog (sHH) signalling pathway may be a downstream of EIF5A in PC cells. Inhibition of EIF5A and sHH signalling pathway could suppress PC cells proliferation and tumour growth. Importantly, EIF5A played an important role in gemcitabine sensitivity for PC.

CONCLUSION

Taken together, our results revealed that EIF5A regulated the proliferation of PC through the sHH signalling pathway and decreased the Gem sensitivity in PC, which provided a novel therapeutic strategy for PC patients.