title: Scutellarin inhibits the growth and invasion of human tongue squamous carcinoma through the inhibition of matrix metalloproteinase-2 and -9 and αvβ6 integrin.
abstract: Scutellarin can inhibit the growth and migration of tongue cancer cells in vitro and can regulate cell adhesion; such agents will be the next generation anticancer therapeutics. In this study, we evaluated the antitumor effects of the scutellarin on human tongue squamous carcinoma (SAS) cell line and investigated its molecular mechanism. To explore the possible mechanisms underlying the antitumor effect of scutellarin, we studied its impact on the growth and invasion of SAS cells xenografted into nude mice, on the expression of MMP-2, MMP-9, integrin αvβ6, and c-JUN, and also on changes in collagen fibers. We observed that the growth of xenograft SAS tumors in nude mice was significantly inhibited by the administration of scutellarin without major adverse effects. Results showed that scutellarin mediated inhibition of tumor cell proliferation, induced apoptosis, and regulated expression of matrix metallo-proteinase (MMP)-2 and -9, and integrin αvβ6 at the mRNA and protein levels in vivo. Moreover, scutellarin regulated the expression of collagen fibers in the tumor microenvironment (surrounding the tumor), thereby inhibiting cell invasion and metastasis. Our in vitro and in vivo studies have shown that scutellarin reduces the expression of MMP-2 and -9, and integrin αvβ6 in SAS cells, possibly through the regulation of expression of transcription factor AP-1. These results suggest that scutellarin can have an anti-tumor therapeutic effect by inhibition of the ability of SAS cells to invade and metastasize.
authors.affiliation: Department of Anatomy, Basic Medical Science College, Harbin Medical University, Harbin 150081, PR China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Li
authors.forename: Dayong
authors.initials: D
authors.lastname: Huang
authors.forename: Zhongxiuzi
authors.initials: Z
authors.lastname: Gao
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Lina
authors.initials: L
authors.lastname: Zhang
authors.forename: Jinhua
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D047310:Apigenin / Q000008:administration & dosage*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005965:Glucuronates / Q000008:administration & dosage*; D006801:Humans; D016023:Integrins / Q000235:genetics* / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D014062:Tongue Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D000951:Antigens, Neoplasm; D005965:Glucuronates; D016023:Integrins; C073878:integrin alphavbeta6; C484876:scutellarin; D047310:Apigenin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9