Terbinafine Inhibits KSR1 and Suppresses Raf-MEK-ERK signaling in Oral Squamous Cell Carcinoma Cells
Abstract:
Terbinafine inhibits the proliferation of many types of cancer cells, but the underlying mechanism remains to be determined. By computer simulation, we found that kinase suppressor of Ras 1 (KSR1) is a possible target of terbinafine. Treatment of human oral squamous cell carcinoma (OSCC) KB cells with either terbinafine or siRNA to knockdown KSR1 reduced proliferation and induced apoptosis, which was accompanied by suppression of the Raf-MEK-ERK pathway. In vivo, KSR1 expression was significantly associated with the clinical staging of OSCC and the smoking habit of patients. Kaplan Meyer survival analysis demonstrated that the cumulative survival time of patients without KSR1 expression was significantly longer than those with KSR1 overexpression. Our data provide the basis for developing terbinafine to treat OSCC.