title: 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.
authors.affiliation: Department of Oral Anatomy and Physiology, China Medical University, Liaoning Province, People's Republic of China. libo919_oral@163.com
authors.forename: B
authors.initials: B
authors.lastname: Li
authors.forename: L
authors.initials: L
authors.lastname: Lu
authors.forename: M
authors.initials: M
authors.lastname: Zhong
authors.forename: X X
authors.initials: XX
authors.lastname: Tan
authors.forename: C Y
authors.initials: CY
authors.lastname: Liu
authors.forename: Y
authors.initials: Y
authors.lastname: Guo
authors.forename: X
authors.initials: X
authors.lastname: Yi
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007624:KB Cells; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009281:Naphthalenes / Q000378:metabolism / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011494:Protein Kinases / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D000077291:Terbinafine
chemical_list: D009281:Naphthalenes; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D011494:Protein Kinases; C097199:KSR-1 protein kinase; D048049:Extracellular Signal-Regulated MAP Kinases; D000077291:Terbinafine