Leflunomide inhibits proliferation and tumorigenesis of oral squamous cell carcinoma

: Oral squamous cell carcinoma (OSCC) is the most prevalent pathological cancer occurring in the head and neck area. Progress has previously been made regarding treatment strategies of OSCC, however the 5‑year survival rate of these patients is only 50%. The present study examined if leflunomide (LEF), a drug primarily used for the treatment of rheumatoid arthritis, exhibited antitumor effects in OSCC. The results demonstrated that LEF inhibited cell proliferation and blocked the cell cycle at the S phase in OSCC cells, with upregulation of cyclin A protein expression. LEF reduced the expression of dihydroorotate dehydrogenase, which is an essential enzyme in the de novo pyrimidine biosynthetic pathway. LEF additionally inhibited colony formation in soft agar and reduced tumor growth in a xenograft model. The results suggested that LEF may act as a potential therapeutic agent in the treatment of OSCC in the future.