Scutellarin inhibits cell migration by regulating production of αvβ6 integrin and E-cadherin in human tongue cancer cells

Abstract

To examine the effect of scutellarin on adhesion and migration of oral squamous cell carcinoma (OSCC), the HSC-4 and SAS human OSCC cells were treated with various concentrations of scutellarin. Scutellarin cytotoxicity was evaluated by MTT assays; migration of tongue cancer cells was assessed by wound healing and Transwell chemotaxis; αvβ6 integrin and E-cadherin expression was assessed by immunofluorescence and reverse transcription polymerase chain reaction. Scutellarin at 75 nM significantly inhibited tongue cancer cell proliferation and at 15 nM, significantly reduced HSC-4 and SAS cell motility by 46.3% and 44%, respectively. Scutellarin inhibited SAS cell adhesion to fibronectin in a dose-dependent manner. However, it had no significant effect on HSC-4 cell adhesion to fibronectin; at the same concentration, HSC-4 cells adhered more strongly to fibronectin than SAS cells. Following treatment with scutellarin, E-cadherin and desmoplakin protein levels were increased, whereas E-cadherin mRNA expression was unchanged; protein levels of αvβ6 integrin were decreased-consistent with the change in αvβ6 integrin mRNA. After a 3 nM scutellarin treatment, levels of desmoplakin in HSC-4 and SAS cells increased by 79.9% and 74.5%, respectively. Scutellarin (3 nM) increased expression of E-cadherin in HSC-4 and SAS cells by 37.9% and 52%, respectively, and decreased the expression of αvβ6 integrin by 45.4% and 47.2%, respectively. This study shows that scutellarin inhibits tumor cell proliferation and migration and regulates cell adhesion in OSCC cells; this may be closely related to up-regulation of E-cadherin and down-regulation of αvβ6 integrin.