Tacrolimus Reduces OSCC Cells’ Proliferation Through Glutamine Metabolism

Objectives: To evaluate the efficacy and the molecular mechanism of tacrolimus(FK506) on OSCC cells.
Methods: CCK8, colon formation assay, the OSCC cell xenograft in nude mice and 4NQO induced OSCC in SD rats were used to explore the role of FK506 for the OSCC cells. Flow cytometry and Western Blot analysis the OSCC cell cycle. Agilent Seahorse XFe96 analysis the metabolism reprogramming of OSCC cells after the treatment of FK506. RNA-seq,ChIP and tandem mass spectrometry found the role of NFAT2/3 regulating glutamine metabolism.
Results: FK506 induces the concentration-dependent proliferation inhibition of OSCC cells in vivo and vitro. Flow cytometry and Western Blot analysis indicate that OSCC cells’ cycle was arrest on GI graph. The metabolism inhibition especially glutamine metabolism after FK506 treatment was been tested by Seahores. NFAT2/3 , as the downstream of FK506, recruites SFPQ and NONO and regulates the transcription of c-Myc to regulate glutamine metolism.
Conclusions: FK506 reduces OSCC cells’ proliferation through NFAT2/3 recruiting SFPQ-NONO complex to regulating glutamine metabolism.